CN102178561A - 125I particle-containing kit and application thereof - Google Patents
125I particle-containing kit and application thereof Download PDFInfo
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- CN102178561A CN102178561A CN201110060076XA CN201110060076A CN102178561A CN 102178561 A CN102178561 A CN 102178561A CN 201110060076X A CN201110060076X A CN 201110060076XA CN 201110060076 A CN201110060076 A CN 201110060076A CN 102178561 A CN102178561 A CN 102178561A
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Abstract
The invention discloses a 125I particle-containing kit and application thereof. The kit comprises 125I particles, bone cement polymethyl methacrylate and a contrast agent. A Banna minipig test animal model implanted by percutaneous vertebroplasty is established. By the kit, a relationship between irradiation dose and time of radiation myelitis caused by short-distance irradiation of the 125I particles is discussed. By the kit, spinal metastatic tumor patients are treated and researched; and after implantation by the percutaneous vertebroplasty, curative effect is improved and postoperative complications are reduced compared with those by the pure percutaneous vertebroplasty.
Description
Technical field
The present invention relates to the medical material field, be specifically related to a kind of containing of percutaneous vertebroplasty implantation that be used for
125Test kit of I particle and uses thereof.Described test kit can be used for the treatment of spinal column metastatic tumor.
Background technology
(percutaneous vertebroplasty is under image documentation equipment monitors PVP) to the percutaneous vertebroplasty, and the puncture of percutaneous vertebral body is injected bone cement to increase vertebral body intensity, and the stable disease vertebral body prevents collapse of vertebra, thereby plays effect such as ease the pain.Because the develop rapidly of intervening equipment in recent years, on the PVP basis new development PKP, PKP is on the PVP basis, the vertebral body that utilizes balloon expandable to subside earlier, push contiguous sclerotin, in vertebral body, create a space, inject bone cement again,, increase vertebral body intensity etc. to recover vertebral height, play releasing or ease the pain etc. acts on [Gangi A, Dieteman TJ, Mortazavir R, et al.CT guided intervential procedures for pain management in the lumboscural spine.Radiographics, 1998,18 (3): 621-637.].When vertebroplasty is applied to open surgery the earliest, be used for strengthening having angiomatous vertebral body.[Galibert P such as French scholar Galibert in 1984, Deramond H, Rosat P, etal.Prelimainary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty.Neurochirurgie, 1987,33 (2): 166-168.] according to surgical operation injection bone cement experience, at first use percutaneous vertebroplasty (percutaneous vertebroplasty, PVP) treatment cervical vertebra cavernous hemangioma has been obtained good analgesic effect, and in reported first in 1987 this technology, nineteen ninety further proposes this technology again and can be used for myeloma, metastatic tumor, the treatment of osteoporotic fracture etc. [Galibert P, Deramond H. Percutaneous acrylic vertebroplasty as a treatment of vertebral angioma as well as painful and debi
The bone cement that is used for vertebroplasty must change its allotment ratio, the monomer that more manys that adding is recommended than producer reduces viscosity to be easy to injection, and do not influence its intensity and hardness [Jasper LE, Deramond H, Mathis JM, et al.The effect of monomer to power ration on the matherial properties of cranioplastic.Bone, 1999,25:27-29.Belkoff SM, Maroney M, Fenton DC, et al.Anin vitro biomechanical evaluation of bone cements used in percutaneous vertebroplasty.Bone, 1999,25:23-26.].The bone cement of clinical use of present stage has two big classes: the 1) bone cement that can be degraded: and the methylol calcium phosphate bone cement (hydroxyapatie, HA) etc.; 2) nondegradable bone cement: acrylic acid bone cement, polymethyl methacrylate (PMMA) etc.[Belkoff SM such as Belkoff, Mathis JM, Erbe EM, et al.Biomechanical evluation of a new bone for use in vertebroplasty.Spine, 2000,25 (9): 1061-1064.] experiment in vitro finds that the methylol calcium phosphate bone cement can not improve vertebral body intensity and hardness.PMMA is the most frequently used bone cement of present PVP.PMMA is a kind of inorganic polymer bone renovating material, mainly be polymerized by polymethyl methacrylate and monomer acrylic acid formicester, belong to traditional bone alternate material, the radiotransparent characteristic of PMMA tool, for strengthening its radiopacity, can suitably add barium, tantalum or tungsten powder [Murphy KJ, Deramond H.Percutaneous verttebbroplasty in benign and malignant dieases (Review) .Neuroimaging Clin N Am, 2000,10 (3): 511-518.].Discovery bone cements such as Cotton inject can cause tumor section or downright bad fully in the tumor body, may have in various degree in the toxicity and its process of setting [Cotton A due to the release heat for PMMA, Dewatr F, Cortet B, et al.Percutaneous vertebroplasty for osteolytic imestastases and myelma:effects of the percentage of lesion filling and the leakage of methymethacrylate at clinical follow up.Radiology, 1996,200 (2): 525-530.].As if the temperature of measuring in the experimentatioies such as Deramand be not enough to produce so effect [Deramond H, Wright NT, Belkoff SM, et al.Temperature elevation caused by bone cement polymerization during vertebroplasty.Bone, 1999,25:17-21.].Therefore have the scholar think the antitumor action of vertebroplasty may be tumor tissues to heat effect than normal structure sensitivity, and the bone cement of injection directly or indirectly stops up tumor vessel, causes the partial necrosis of tumor.Percutaneous vertebroplasty wound is little, it is pain caused effectively to alleviate the molten bone metastatic tumor of vertebral body, aggressive hemangioma, myeloma and osteoporosis, increase vertebral body intensity, improve spinal stability, although its clinical practice time is not long, because of its safety and effect are remarkable, obtained abundant affirmation, have a extensive future.Percutaneous kyphoplasty art (the percutaneous kyphoplasty of nearest report, PKP) be to utilize the expandable bone packer to strut compression vertebral body and in vertebral body, set up a space and inject high viscosity bone cement [Hide IG then, Gangi A.Percutaneous vertebroplasty:history, technique and current perspectives.Clinical Radiology, 2004,59 (6): 461-467.].This method combines the advantage of protruding orthopaedy in back and PVP, both can rebuild the compression vertebral height, correct the vertebral body kyphosis deformity, can play pain relieving again, reinforce vertebral body and keep the effect of function, and can recover the height of vertebral body osteoporosis compression fracture or wound compression fracture vertebral body.Because the protruding orthopaedy in back has been created enough big space and has been injected high viscosity PMMA in the compression vertebral body, thereby has prevented the generation of bone cement seepage complication.
125The I radioactive particle also is called the particle cutter, is a kind of very advanced miniature sealed radioactive source.Adopt
125Brachytherapy is the application of atomic energy physics on clinical medicine between I particle tissue, is one of high-tech treatment means of modern medicine.
125The I radioactive particle is implanted all has significant curative effect to carcinoma of prostate, nasopharyngeal carcinoma, rectal cancer, cancer of pancreas,
125Brachytherapy has the characteristics of height conformal therapy between I radioactive particle implanting tissue, have Wicresoft simultaneously, damage is slight, complication is few, use advantages such as easy, obtaining satisfactory effect [Ebara S aspect some malignant entity tumors of treatment, Katayama N, Tanimoto R, Edamura K, et al.Iodine-125 seed implantation (permanent brachytherapy) for clinically localized prostate cancer.Zhang FJ, Li CX, Wu PH, et al.Radioactive seed 125I implantation in treating recurrence and metastasis after liver transplantation in hepatoma.Zhonghua Yixue Zazhi 2007; 87:956-959.Acta Med Okayama 2008; 62:9-13.Darakchiev BJ, Albright RE, Breneman JC, et al.Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme.J Neurosurg 2008; 108:236-242.Martinez-Monge R, Pagola M, Vivas I, et al.CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) .Lung Cancer 2008; 61:209-213.].
In the percutaneous vertebroplasty, the exploitation of new type of safe, economy, good biocompatibility, bone cement that toxicity is little has great importance, and the present invention has explored a kind of novel bone cement.
Summary of the invention
The present invention has designed a kind of containing of percutaneous vertebroplasty implantation that be used for
125The test kit of I particle is to realize that humans and animals is carried out the effect that particle is implanted disease treatment.
Particularly, the present invention relates to a kind of test kit that the percutaneous vertebroplasty is implanted that is used for, comprise described
125The I particle, bone cement, contrast agent.Preferably, described bone cement be polymethyl methacrylate (Polymethylmethacrylate, PMMA).In addition, described contrast agent is preferably 76% Injectio Meglumni Diatrizoatis Composita, packing 20ml/15.2g, and amount of iodine is 370mg/ml.This test kit can also comprise: stereotype and preventer, screw type syringe pressue device, vertebral plasty puncture needle, surgical mallet, disposable sterilized syringe, particle implanting gun and disposable particle source delivery needle.
The present invention relates to a kind of on the other hand
125The I particle is characterized in that:
125The I particle is the iodine-125 sealed seed source, and the source core of sealed seed source is for containing radionuclide
125The filamentary silver of I, involucrum are the high purity titanium pipe of electron beam or laser soldering seal.The amplification imaging systems inspection of its outward appearance, the end points welding is slick and sly, the no concave-convex injustice, the sealing atresia, the long 4.5mm of sealed seed source, diameter 0.8mm, average energy 27.4-35.4Kev, half-life 60.1d, half value layer 0.025mm Pb, knitting the ability of wearing is 17mm, surface activity is the 1.00mCi/ grain, 135 days effect duration, 1 μ Ci=37MB, physical half time (T1/2)=60.1 day.
The invention still further relates to described
125I particle and described test kit get purposes, preferably are used for the associating of percutaneous vertebroplasty in preparation
125Application in the instrument that the I particle is implanted and/or the application in the instrument of preparation treatment tumor.Described tumor can be various types of tumors, wherein is preferably the spinal column metastatic tumor.
For the content of further studying and checking the present invention asks for protection, percutaneous vertebroplasty (Percutaneous Vertebroplasty, PVP) associating have been set up at embodiment 1
125The version that the I particle is implanted is received miniature pig experimental animal model, implement under the research TPS treatment plan PVP and
125The incidence rate and the preventive measure thereof of I particle implant surgery complication.Inquire into
125The exposure dose and the time relation of the caused radiation myelitis of I particle irradiation at short distance.At embodiment 2, utilize novel test kit, by spinal column metastatic tumor patient is treated, analysis-by-synthesis its in treatment spinal column metastatic tumor curative effect, post-operative complication and to the influence of important organ function, further inquire into novel agent box of the present invention in advantage in conjunction with implantation treatment spinal column metastatic tumor.
Description of drawings
Fig. 1 receives thoracic vertebra and the corresponding segments of spinal cord sketch map of miniature pig for version, wherein among the figure from top to bottom second joint be the T13 vertebral body
Fig. 2 is
125I particle structure sketch map.The source core of sealed seed source is for containing radionuclide
125The filamentary silver of I, involucrum are the high purity titanium pipe of electron beam or laser soldering seal.
Fig. 3 novel agent box is implanted version and is received the sketch map of miniature pig T13 vertebral body.Wherein A figure is a sketch map before the operation; B figure is an operation back sketch map.
Fig. 4 novel agent box vertebral body is implanted into and hinders version and receive in the miniature pig art and postoperative DSA sheet finding.Wherein A figure is a DSA sheet in the operation; B figure is an operation back DSA sheet.
Fig. 5 is implanted into result of study figure for the molten bone metastatic tumor of vertebra patient's canalis spinalis.Adopt the simple PVP treatment in novel agent box treatment of the present invention back to have better clinical effectiveness.
Embodiment 1 edition receives the canalis spinalis of miniature pig and is implanted into experiment
One, material and instrument
1.1 experiment material and experimental apparatus
Version is received miniature pig; Bone cement;
125The I particle; Be used for the novel agent box of percutaneous vertebroplasty, comprise
125The I particle, bone cement, contrast agent.Stereotype and preventer, screw type syringe pressue device, vertebral plasty puncture needle, surgical mallet, disposable sterilized syringe, particle implanting gun and disposable particle source delivery needle.
1. laboratory animal
The adult healthy version is received 12 of miniature pigs, and body weight 20-25kg (average 22.7kg) is female.Unming Medical College's Experimental Animal Center provides and raises.Before the experiment, in 1 week of breeding observing, diet, two just, motion is normal.Preliminary experiment finds that T13 is best experiment vertebral body sections (Fig. 1).
2. experiment material
1) seed source:
125The I particle be the iodine-125 sealed seed source (hereinafter to be referred as
125The I particle), the source core of sealed seed source is for containing radionuclide
125The filamentary silver of I, involucrum are the high purity titanium pipe of electron beam or laser soldering seal.Outward appearance amplification imaging systems inspection, the end points welding is slick and sly, no concave-convex injustice, sealing atresia.The long 4.5mm of sealed seed source, diameter 0.8mm, average energy 27.4-35.4Kev, half-life 60.1d, half value layer 0.025mm Pb, knitting the ability of wearing is 17mm.Surface activity is the 1.00mCi/ grain, 135 days effect duration, 1 μ Ci=37MB.Physical half time (T
1/2)=60.1 day.Its structure is seen Fig. 2.
2) stereotype: thickness=1.5mm, shield test reactor detects before testing, and can shield fully
125I corpuscular radiation line.With this material shielding pig, tank body crack=L (T
13Horizontal spinal cord width), vertebral height=H (T
13Horizontal spinal cord height).
3) bone cement: polymethyl methacrylate (Polymethylmethacrylate, PMMA).
4) contrast agent: 76% Injectio Meglumni Diatrizoatis Composita, packing 20ml/15.2g, amount of iodine is 370mg/ml.
3. experimental apparatus
1) radiotherapy treatment planning system (treatment planning system, TPS)
Be used for the preceding planned of art, operation implantation and the protection of radioactive particle brachytherapy.By the TPS treatment planning systems, with graphic materials such as experiment pig CT, MRI input computer, computer calculates the dose distribution of radiotherapy according to the requirement of these data and experiment target area, and therapeutic scheme is optimized selection.TPS can accurate reconstruction target target area three-dimensional configuration, accurately design position, quantity that particle is implanted, and, realize the suitable capable radiotherapy of target target area in conjunction with dissecting the implantation approach that is provided with.Wherein the TPS software system is the core key of this system, by this computed in software, can clearly show particle implantation spatial distribution and dosage distribution curve.
2) active nucleus activity detector (model: CRC-15R)
This instrument is made up of probe and main frame, can measure to comprise
125I uses nucleic always in tens kinds of interior nuclear medicine, resolution 0.01 μ Ci, range ability: 0.01 μ Ci-8Ci, certainty of measurement: 1-2% ± 1%, energy of response: 25Kev-3Mev, repeatability error :≤± 0.5%.
Three, experimental technique
3.1 zoopery
Divide into groups according to the randomly assigne animal: novel agent box of the present invention (
125I particle+bone cement) vertebral body is implanted into group 6 examples (A group) (Fig. 3),
125I particle canalis spinalis is implanted into group 6 examples (B group), and postoperative is all observed 4 half-life (8 months).
Medicine: pentobarbital sodium: China Medicine (Group) Shanghai Chemical Reagent Co., produces, 25g/ bottle, lot number F20000642.Configuration pentobarbital sodium solution 2.5%.Tube-sealing solution: situ configuration, heparin sodium 12500U is dissolved in the 250ml normal saline.Version is received miniature pig auricular vein and is kept somewhere intravenous needle.According to 25mg/kg dosage, the induced anesthesia of intravenous injection pentobarbital sodium, 1ml/15min keeps anesthesia.Behind each administration of anaesthesia, with the heparin sodium aqua tube sealing.
3.2 the particle activity accumulated dose that target target area and expection are implanted
The present software that uses is according to the Rapid Dose Calculation system editor's of classics.USA New York Memorial Sloan-Kettering Caner Cener once drew
125The row of I particle are separated figure, and row are separated figure and described MPD.At first obtain three axial target sizes, calculate average-size afterwards.The total activity that particle is implanted and the relation of size can be obtained according to mathematical formulae.Formula is: population=[(length+wide+thick/3) * 5] sub-activity of the every granule of ÷.The suggestion of several seminar, it is inappropriate utilizing row to separate figure accurate Calculation total activity, suggestion increases by 20～30% total activities.
A group novel agent box vertebral body is implanted into the target district and is positioned at T13 vertebral body body rear flank portion, is spherical shape, diameter=1.0cm.Target district length and width, the thick 1cm that is in this experiment, single piece of corpuscular radiation activity is 1mCi, according to
125I particle close-range treatment clinical dosage calculates formula, ÷ 1=5 of population=[(1+1+1)/3 * 5] that definite expection is implanted; Number of particles is implanted in the intralesional expection increases by 30%, so the target target area is implanted 8 altogether,
125I particle accumulated dose=8 * 1.0=8.0mCi.
The B group
125I particle canalis spinalis is implanted into the target area and is positioned at the right front sidepiece of T13 canalis spinalis.Canalis spinalis is implanted into
125I particle accumulated dose=8 * 1.0=8.0mCi.
3.2 treatment plan design before the art
With pig T
13The CT image,
125In the physics data input TPS of I particle, automatically generate treatment plan by this systems soft ware, determine target area prescribed dose (Prescription Dose according to tumor histology's type, PD), coupling periphery dosage (matched Peripheral Dose, MPD), (minimumPeripheral Dose is mPD) with the spatial distribution coordinate of expecting that particle is implanted for minimum circumference dosage.Prescribed dose 80Gy implants source strength 3.00x10
7Bq, D is calculated in the postoperative checking
90(90% target dose) and maximum percent dose (mPD).
What this experiment was different from other soft tissue neoplasms treatment plan is: particle only is distributed in tumor range edge or top layer, the inner no distribution of particles of target area tumor kitchen range; Because osseous tissue obviously greater than soft tissue, obviously dwindles about 0.2cm～0.3cm so implant spacing between particle to the attenuation effect of ray.
3.3 version is received the canalis spinalis of miniature pig and is implanted into experiment
Select the adult healthy version to receive 12 of miniature pigs, be divided into two groups of A, B: A group at random: the novel agent box (
125I particle+bone cement) vertebral body is implanted into 6 of groups; The B group:
125I particle canalis spinalis is implanted into 6 of groups.
A group simulation tumor kitchen range (target target area) is rear portion, T13 vertebral body right side, is spherical shape, and diameter=1.0cm implants vertebral body target target area by TPS treatment plan row novel agent box before the art,
125The I particle is inserted several 8 (8.0mci)/vertebral bodys, predose 2.92cGy/h/ particle, tumor periphery coupling dosage (MPD) 80Gy～100Gy, bone cement bolus dose 0.8～1.3ml, average 1.0ml.After the source intravenous anesthesia of pentobarbital sodium ear, experiment pig is got the ventricumbent position, preserved skin, sterilization, shop aseptic towel, DSA machine location T13 vertebral body and pedicle of vertebral arch body surface projection, sharp knife punctures point of puncture skin, and puncture needle enters vertebral body through vertebral body side approach (becoming 20 °～30 ° angles with coronalplane) in the pedicle of vertebral arch basilar part, needle point arrives at the target target area, and the DSA radiography shows that puncture position is good.According to the TPS designing requirement, will
125The I particle is three-dimensional dot matrix and implants.In powder: liquid: contrast agent ratio allotment in 3: 2: 1 bone cement, inject to the target area in " toothpaste phase ", constantly adjust the needle point direction when injecting bone cement, bone cement is filled be tending towards good, reduce the seepage incidence rate.Bone cement bolus dose 0.8～1.3ml, average 0.9ml.CT scan confirms the distribution effect.A group novel agent box vertebral body is implanted in the art and postoperative DSA sheet is seen Fig. 4.
The B group
125I particle canalis spinalis is implanted into the target area and is positioned at the right front sidepiece of T13 canalis spinalis,
125The I particle is inserted several 8 (8.0mci)/heads, predose 2.92cGy/h/ particle, tumor periphery coupling dosage (MPD) 80Gy～100Gy.The postoperative CT scan is observed bone cement and is reached
125I distribution of particles situation.Evaluation experiment pig function of spinal nerves.After the source intravenous anesthesia of pentobarbital sodium ear, experiment pig is got the ventricumbent position, preserved skin, sterilization, the shop aseptic towel, DSA machine location T13 vertebral body and pedicle of vertebral arch body surface projection, sharp knife punctures point of puncture skin, under template-directed, through vertebral body side approach (becoming 20 °～30 ° angles with coronalplane), enter canalis spinalis in vertebral body-pedicle of vertebral arch point of interface, it (is canalis spinalis that needle point is positioned at canalis spinalis antetheca rear, not Spinal Cord and surperficial dura mater structure thereof), DSA machine perspective 76% cardiografin radiography down shows that puncture position is good.The lancet channel that wears long, (being between dura mater-canalis spinalis antetheca) implants in canalis spinalis
1258 pieces on I particle (8.0mci).
4 half-life (8 months) back A group gets the T13 vertebral body and the spinal cord specimen is carried out pathological examination, and the B group is got the horizontal spinal cord specimen of T13 and carried out pathological examination.
3.4 animal feeding and observation
After the anesthesia recovery, animal send unming Medical College's Experimental Animal Center conventional raising.Observe the animal diet followed and the mental status every day; Observe weekly animal motion (especially hind leg), wag the tail, two just situations, and note down.With reference to the improvement Tarlov scoring of ASIA (ASIA) staging, Yan Jianchun etc. improve, and measure the two hind leg functions of pig, are divided into the 0-5 branch, and mark is high more, and function is good more.
ASIA (ASIA) staging classification
3.5 test experience method
1.CT scanning is estimated
Check CT and three-dimensional reconstruction in postoperative half an hour, February, August.
2. nuclear magnetic resonance (MRI) is checked
Adopt Siemens Sonata type 1.5T superconduction nuclear-magnetism machine, the gradient field intensity is 25mT/m, the body coil imaging, and scanning process adopts ecg-gating, and scan method comprises routine MRI, Contrast-enhanced MRI.MRI scanning is adopted half Fourier to gather the single-shot spin-echo sequence, is disturbed phase place radio-frequency pulse gradin-echo, real stable state precession fast imaging sequence.Sweep parameter, TR/T is respectively (900～1100) ms/120ms, (100～120) ms/4.7ms, 3.76ms/1.88ms, bed thickness 2～6mm, the layer apart from 0.2mm～1.8mm, scanner field (FOV) 320～400mm.The scanning position comprises transverse axis position, sagittal plain, crown position and left anterior oblique position.Adopt SEEPI multiple excitation diffusion-weighted imaging (MS DWI) sequence scanning, use automatic shimming, fat technology and self-navigation alignment technique in the scanning, sweep parameter is: TR is 2beats (about 1600ms), and TE 18ms or the shortest adopts the PPU technology.The imaging orientation is divided into sagittal plain and axle position, is to add the responsive gradient of disperse on frequency coding (M) direction at level selection (S), position coding (P) and readout gradient respectively, and the disperse gradient factor (gradient factor) b value is 500s/mm
2Calculating average surface dispersion coefficient (apparent diffusion coefficient, ADC) the ADC value of value and each disperse gradient direction, thus calculate relative ADC value, the anisotropy of reflection spinal cord disperse.
3.T13 vertebral body trailing edge radiation activity detects
The A group is removed appendix of vertebra, only keeps the vertebral body body, inserts in the self-control shielding pig, and the vertebral body trailing edge is close to the place, crack, only allows the lonizing radiation of vertebral body trailing edge to pass through, and thoroughly masks the lonizing radiation that remaining surface is disengaged.Vertebral body-pig places in the active nucleus activity detector and detects, and obtains the apparent radiation activity of vertebral body trailing edge.
Calculate exposure dose rate and spinal cord surface irradiation dosage according to following formula
1) exposure dose rate calculates
Simple grain according to the document recommendation
125I particle close rate in aqueous medium is calculated formula, calculates the suffered exposure dose rate of certain 1 P (r θ) in the particle space of living in.This experiment is considered as radioactive source with target target area-particle complex, and the spinal cord surface is the P point.Calculate the suffered exposure dose rate of spinal cord surface point (r θ) in the space of living in, target target area, θ=90 °.Computing formula is as follows:
D
(0)＝A
0*1.27*Λ*g
(r)*F
(rθ)/r
2
In the formula: A
0Be the apparent activity of sample (mCi); Λ is
125The dose rate constant of I particle is for a certain specific
125I seed source, the close rate constant is fixed, the BT-125-1 type
125This value in I seed source is 1.06; R is the beeline of target district center to the spinal cord surface point for the distance (cm) of a particle surrounding space point P to the particle center in this experiment; g
(r)Be dose function radially, represent in the medium absorption and scattering effect along the particle transverse axis; F
(r θ)Be anisotropy constant, this experiment g
(r), F
(r θ)Research measured value with reference to Sun Liang [10].D
(0)Initial exposure dose rate (cGy/h) during for the implantation particle.
2) spinal cord surface irradiation Rapid Dose Calculation
Calculate the spinal cord surface according to following formula and implanting the irradiation accumulated dose of particle in 4 half-life.
D
(T)＝D
(0)*T
1/2*1.443*[1-e
-T*0.693/T1/2]
In the formula: D
(T)Be that certain point is being implanted the irradiation accumulated dose of particle T in the time in the tissue, unit is cGy; D
(0)Refer to this predose rate when implanting particle, unit is cGy/h; T
1/2Be
125The physical half time of I particle; E is a natural constant.
4. gather spinal cord and vertebral body specimen
With two groups of experiment pig general anesthesias, the skin that is vertically cut the experimental section spinal column by the back exposes spinous process and the other muscular tissue of spinal column, to both sides sharp property separation soft tissue, peel off and appear the spinous process of testing spinal segments, with the excision of structures such as vertebral plate, adnexa, the spinous process except that T11-L1, vertebral plate are stung in rongeur, appear spinal cord, glutaraldehyde is spinal cord fixedly, puts to death animal, the spinal cord at two ends and the nerve root of both sides about cutting off, cut the horizontal spinal cord of T13, then with the vertebral body en bloc resection of corresponding spinal column segment.
5. pathology detection method
1) specimen is observed substantially
Put to death animal in 8 months respectively at postoperative.Take out the T13 vertebral body, the A group is cut open in the middle of specimen, observes implantable bone cement and reaches
125Particle-filled and the distribution situation of I.Spinal cord that takes out and vertebral body place 10% formalin fixing immediately, and after 48 hours, spinal cord can section statining.Vertebral body carries out section statining again through 1% nitric acid decalcification 72 hours when can thrust in the vertebral body more smoothly with pin after.
2) specimen section statining
Spinal cord specimen: choose the corresponding spinal cord section in T13 vertebral body position and make section.The vertebral body specimen: select T13 to make section, slice thickness 4mm, two kinds of materials all adopt HE dyeing.
3) perspective Electronic Speculum (EM) is observed
3.5% glutaraldehyde is fixed, and is fixing behind 1% osmic acid, the gradient dehydration step by step of ethanol, acetone, epoxy resin 618 infiltrations, embedding, semithin section, piece is repaiied in the light microscopic location, the section of Leica-R type ultramicrotome, the two dyeing of lead citrate-acetic acid uranium, JEM-1011 transmission electron microscope observing.
6. statistical analysis
All measurement datas are used normal distribution-test, the person's of meeting data all use mean ± standard deviation (
) expression.Use SPSS 11.5 statistical package analyses.Measurement data adopts the t check, and enumeration data adopts x
2Check.
Four, experimental result
4.1
125I particle implanting result
Two groups of laboratory animals are implanted populations and TPS, and to calculate population identical, and the immediate postoperative CT scan is used TPS and carried out particle and rebuild, and draws the average exposure dose A group of accepting the target area by the volume dose rectangular histogram and is 120.2Gy, mPD80.1Gy, D
9090.2Gy, D
90＞mPD.The B group is 152.2Gy, mPD85.3Gy, D
9093.2Gy, D
90＞mPD.
4.2 animal experimental model observed result
1. the postoperative animal is observed:
Two groups of experiment pig are all performed the operation smoothly, and postoperative is recovered naturally, recover proper motion, and postoperative all gives penicillin 8,000,000 IU intravenous injection anti-inflammatory treatments 3 days.
A group experiment pig is all finished the implant surgery of novel agent box, confirms that through postoperative CT tomoscan distribution of particles meets model and the source requirement of TPS cloth, and 1 routine small amount of bone cement is to the other seepage of vertebra, and 1 routine small amount of bone cement seepage in canalis spinalis does not have other severe complication.4 half-life of clinical follow (8 months), acroparalysis, the just obstacle symptom of minimizing and two of wagging the tail after all occurring.
The B group is also finished smoothly
125I particle particle canalis spinalis is implanted into operation, and particle is concentrates point-like to be distributed in the preceding right side of canalis spinalis, and the CT tomoscan confirms that distribution of particles is in epidural.Clinical follow 3 days does not see that sign appears in operation on spinal cord damage symptom.1 experiment pig wherein, comparatively serious abdominal distention symptom appearred on the 2nd day in postoperative, disposed through transfusion, aerofluxus, and postoperative recovered normal diet on the 3rd.Observe to raise 4 half-life (8 months), wherein right side hind leg paresis paralysis appears in 4 (4/6), and minimizings of wagging the tail do not have obvious two just obstacles, and feed reduces, when wherein 1 pig is observed 8 months with tangible abdominal distention symptom.
2. two groups of pig improvement Tarlov scoring changes
B group scoring is 2.57 ± 0.36, and the A group is 5.00 ± 0.00, two groups and compares that there were significant differences (P＜0.05).
3.CT scanning is estimated
The capable T13 vertebral body of each model postoperative 15min 2mmCT thin slice scan is confirmed that bone cement and distribution of particles meet modeling demand in the above-mentioned model.The A group is observed bone cement and is reached
125The I particle is good in Intrapyramidal distribution, sees that bone cement mainly is distributed in the vertebral body spongy bone part, is bulk or patch shape, and visible sometimes anterior spinal veins develops.1 routine small amount of bone cement is to the other seepage of vertebra, 1 routine small amount of bone cement seepage in canalis spinalis.The B group is seen
125The I particle is positioned at outside the canalis spinalis endosclerite, does not have displacement, and spinal cord is not seen damaging change.
4. measure the geometric data of vertebral body
The long L of spinal cord maximum transverse diameter (only limiting to A organizes) that utilizes the CT Survey Software to measure the particle district to face, target area center are to beeline r, the T13 vertebral body section spinal cord height H of spinal cord leading edge.
5. measure the geometric data of canalis spinalis
In the canalis spinalis particle implantation group measure population center and spinal cord lateral margin angle α and with the corresponding spinal cord section of T13 on the angle theta of lower edge, concrete grammar is seen Figure 14-16.Determining of Figure 17 R ' point: as shown in the figure
125I particle-irradiation zone, the area of the area=red area of blue region, then R ' puts to the distance=r of particle center, wherein r=SQRT ((L/2)
2+ (H/2)
2)/SQRT (2).
6.MRI estimate
Pathological changes is early stage, shows on the MRI image that spinal cord slightly increases slightly, and smooth surface, subarachnoid space are narrow slightly.Spinal cord is high signal on the T2WI image, and gray nucleus on the axis location image " H " is fuzzy, and unclear with white matter structure boundary on every side, some case grey matter " H " shape shows unclear; T1WI is slightly low signal or shows no obvious abnormalities signal change, and as seen spinal cord smooth surface, enhanced ct scans do not have or the mile abnormality contrast strengthens, and the pathological changes spinal cord increases slightly; DWI shows that spinal cord is high signal and ADC reduces.Pathological changes mid-term, spinal cord can obviously increase slightly, smooth surface, and subarachnoid space is narrow.On T1WI and T2WI picture, all be inhomogeneous signal change, this be because progressive stage each position of pathological changes spinal cord be in different developing periods.The visible steatosis of operation vertebral body, T1WI, T2WI evenly are high signal, and be obvious with the normal marrow contrast.Pathological changes late period, myelatrophy or part myelomalacia, smooth surface or owe smooth, subarachnoid space broadening.The spinal cord of atrophy signal on T1WI and T2WI picture changes not obvious, and softening kitchen range is the long T2 of long T1 and changes.As seen gray nucleus " H " and white matter smaller volume on every side on the T2WI picture of axle position, obvious with white matter.Operation vertebral body steatosis is more obvious, is tangible high signal especially on the T1WI picture.Situation clear displays on MR sagittal plain image such as spinal cord injury length, swelling and atrophy, myelatrophy signal on T1WI and T2WI picture changes not obvious.
7. calculate spinal cord surface irradiation dosage
Described according to method, the geometric data, the detection A that measure T13 vertebral body and particle spatial distribution organize the apparent radiation activity of vertebral body trailing edge, and B group spinal cord surface irradiation dosage the results are shown in following table.
The apparent radiation activity of table 1A group vertebral body experimental group, exposure dose rate and spinal cord surface irradiation accumulated dose result
Table 2B group spinal cord dosage rate and spinal cord surface irradiation accumulated dose result
A group experiment pig is all finished the implant surgery of novel agent box, confirms that through postoperative CT tomoscan distribution of particles meets model and the source requirement of TPS cloth, and 1 routine small amount of bone cement is to the other seepage of vertebra, and 1 routine small amount of bone cement seepage in canalis spinalis does not have other severe complication.4 half-life of clinical follow (8 months), acroparalysis, the just obstacle symptom of minimizing and two of wagging the tail after all occurring.The B group is also finished smoothly
125I particle canalis spinalis is implanted into operation, and particle is concentrates point-like to be distributed in the preceding right side of canalis spinalis, and the CT tomoscan confirms that distribution of particles is in epidural.Clinical follow 3 days does not see that sign appears in operation on spinal cord damage symptom.1 experiment pig wherein, comparatively serious abdominal distention symptom appearred on the 2nd day in postoperative, disposed through transfusion, aerofluxus, and postoperative recovered normal diet on the 3rd.Observe to raise 4 half-life (8 months), wherein right side hind leg paresis paralysis appears in 4 (4/6), and minimizings of wagging the tail do not have obvious two just obstacles, and feed reduces, when wherein 1 pig is observed 8 months with tangible abdominal distention symptom.B group improvement Tarlov scoring is 2.57 ± 0.36, and the A group is 5.00 ± 0.00, two groups and compares that there were significant differences.Obduction finds that A organizes the vertebral body tangent plane and sees that bone cement is positioned at vertebral body behind the sacrifice of animal, and hard closely the fusion with bone structure of matter is difficult to separate, in the visible vertebral body
125The I distribution of particles.Under the mirror disperse of visible bone cement droplet between pig vertebral body spongy bone in.A group spinal cord overall structure is normal substantially, and white matter is not seen obvious fiber swelling, and the grey matter structure is clear.Down visible " oversleeve " sample of B group myelopathy microscopy changes, bites the neuron phenomenon, cell liquefaction and necrosis, neurocyte degenerative atrophy, capillary endothelium degeneration.
Embodiment 2 novel agent boxes are applied to tumor the patient
One, experimental technique
1. the molten bone metastatic tumor of vertebra patient's canalis spinalis is implanted into research
With the molten bone metastatic tumor of 80 routine vertebras patient, be divided into simple PVP at random and organize 40 examples, the PVP associating
125I particle implantation group (therapeutic alliance group) 40 examples.Simple PVP group is to lead percutaneous puncture down at the DSA power traction, bone cement is expelled to suffers from the vertebra.The therapeutic alliance group is that the novel agent box (is united in the PVP art
125The I particle) implants.
2. skeletonization spinal column metastatic tumor patient's canalis spinalis is implanted into research
42 routine skeletonization spinal column metastatic tumor patients are implemented the PVP associating
125I particle implantation is observed clinical efficacy and untoward reaction.
Two, experimental result
1. the molten bone metastatic tumor of vertebra patient's canalis spinalis is implanted into research
Novel agent box treatment group is alleviated (CR) 0 example fully, and part is alleviated (PR) 36 examples (90.0%), no change (NC) 4 examples (10.0%), and progress (PD) 0 example (0%), clinical yield is 100%.Simple PVP group CR 0 example, PR 31 (77.5%), NC 7 examples (17.5%), PD 2 examples (5.0%), clinical yield is 95.0% (Fig. 5).The two groups of clinical yield comparing differences in treatment back have statistical significance.Novel agent box treatment group KPS scoring (92.5 ± 7.1) divides, and simple PVP group KPS scoring (87.7 ± 7.3) divides, and all divide than (68.9 ± 7.9) before the art and (69.4 ± 8.3) and obviously increase, and two groups of comparing differences has statistical significance (P＜0.05).Therapeutic alliance group TTP is 9.0 months, and simple PVP group TTP is 8.9 months.
2. skeletonization spinal column metastatic tumor patient's canalis spinalis is implanted into research
42 examples, 89 joint vertebral body operations are succeedd, every joint vertebral body injection bone cement 1～5ml, thoracic vertebra average out to 2.8ml, lumbar vertebra average out to 3.1ml.Postoperative X line sheet and CT examination show that all patients all obtain the stable of spinal column.Followed up a case by regular visits to 6 months～5 years, 41 examples (97.6%) patient patient postoperative low-back pain obviously alleviates or disappears, and 1 example (2.4%) is improved not obvious, and perioperatively VAS scoring and KPS scoring comparing difference have statistical significance (P＜0.05).The mean survival time of carcinoma of prostate is 18 months in the follow-up period, and the mean survival time of pulmonary carcinoma is 9 months, and the mean survival time of breast carcinoma is 18 months, and comparing difference has statistical significance (P=0.001).
Claims (8)
1. one kind contains
125The test kit of I particle is characterized in that: described test kit comprise bone cement,
125I particle and contrast agent.
2. test kit according to claim 1 is characterized in that, described bone cement is a polymethyl methacrylate.
3. test kit according to claim 1 and 2 is characterized in that, described contrast agent is 76% Injectio Meglumni Diatrizoatis Composita, packing 20ml/15.2g, and amount of iodine is 370mg/ml.
4. one of any described according to claim 1-3
125The I particle is characterized in that,
125The I particle is the iodine-125 sealed seed source, and the source core of sealed seed source is for containing radionuclide
125The filamentary silver of I, involucrum are the high purity titanium pipe of electron beam or laser soldering seal.
5. according to claim 4
125The I particle is characterized in that, the amplification imaging systems inspection of its outward appearance, the end points welding is slick and sly, no concave-convex injustice, sealing atresia, the long 4.5mm of sealed seed source, diameter 0.8mm, average energy 27.4-35.4Kev, half-life 60.1d, half value layer 0.025mmPb, knitting the ability of wearing is 17mm, surface activity is the 1.00mCi/ grain, 135 days effect duration, 1 μ Ci=37MB, physical half time (T
1/2)=60.1 day.
6. one of any described test kit of claim 1-5 is used for the associating of percutaneous vertebroplasty in preparation
125Application in the instrument that the I particle is implanted.
7. the application of one of any described test kit of claim 1-5 in the instrument of preparation treatment tumor.
8. application according to claim 7 is characterized in that, described tumor is the spinal column metastatic tumor.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2208423Y (en) * | 1994-10-11 | 1995-09-27 | 王兆华 | Image-display sphere bag inflatable dilator |
| CN1307907A (en) * | 2001-01-18 | 2001-08-15 | 中国科学院上海原子核研究所 | Iodine-125 seed medicine for intervention treatment and its preparation |
| CN2905096Y (en) * | 2006-01-01 | 2007-05-30 | 张德祥 | Catheter for implanting I125 source into canals |
| CN101072600A (en) * | 2004-11-15 | 2007-11-14 | 科丰公司 | System and method for delivering a therapeutic agent for bone disease |
| US20100196268A1 (en) * | 2008-02-15 | 2010-08-05 | Isotherapeutics Group Llc | Compositions and methods for treatment of tumors by direct administration of a radioisotope |
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2011
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|---|---|---|---|---|
| CN2208423Y (en) * | 1994-10-11 | 1995-09-27 | 王兆华 | Image-display sphere bag inflatable dilator |
| CN1307907A (en) * | 2001-01-18 | 2001-08-15 | 中国科学院上海原子核研究所 | Iodine-125 seed medicine for intervention treatment and its preparation |
| CN101072600A (en) * | 2004-11-15 | 2007-11-14 | 科丰公司 | System and method for delivering a therapeutic agent for bone disease |
| CN2905096Y (en) * | 2006-01-01 | 2007-05-30 | 张德祥 | Catheter for implanting I125 source into canals |
| US20100196268A1 (en) * | 2008-02-15 | 2010-08-05 | Isotherapeutics Group Llc | Compositions and methods for treatment of tumors by direct administration of a radioisotope |
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| 杨祚璋等: "脊柱转移癌经皮椎体成形术联合125I粒子植入治疗", 《中华放射医学与防护杂志》, vol. 26, no. 2, 25 April 2006 (2006-04-25), pages 178 - 179 * |
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