Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy.

A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary ß particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction.

Comparison of MRI pulse sequences in defining prostate volume after permanent implantation.

PURPOSE: To determine the relative value of three MRI pulse sequences in defining the prostate volume after permanent implantation. METHODS AND MATERIALS: A total of 45 patients who received a permanent 125I implant were studied. Two weeks after implantation, an axial CT scan (2 mm thickness) and T1-weighted, T1-weighted fat saturation, and T2-weighted axial MRI (3-mm) studies were obtained. The prostate volumes were compared with the initial ultrasound planning volumes, and subsequently the CT, T1-weighted, and T1-weighted fat saturation MRI volumes were compared with the T2-weighted volumes. Discrepancies in volume were evaluated by visual inspection of the registered axial images and the registration of axial volumes on the sagittal T2-weighted volumes. In a limited set of patients, pre- and postimplant CT and T2-weighted MRI studies were available for comparison to determine whether prostate volume changes after implant were dependent on the imaging modality. RESULTS: T1-weighted and T1-weighted fat saturation MRI and CT prostate volumes were consistently larger than the T2-weighted MRI prostate volumes, with a volume on average 1.33 (SD 0.24) times the T2-weighted volume. This discrepancy was due to the superiority of T2-weighted MRI for prostate definition at the following critical interfaces: membranous urethra, apex, and anterior base-bladder and posterior base-seminal vesicle interfaces. The differences in prostate definition in the anterior base region suggest that the commonly reported underdose may be due to overestimation of the prostate in this region by CT. The consistent difference in volumes suggests that the degree of swelling observed after implantation is in part a function of the imaging modality. In patients with pre- and postimplant CT and T2-weighted MRI images, swelling on the T2-weighted images was 1.1 times baseline and on CT was 1.3 times baseline, confirming the imaging modality dependence of prostate swelling. CONCLUSION: Postimplant T2-weighted MRI images provided superior prostate definition in all critical regions of the prostate compared with CT and the other MRI sequences tested. In addition to defining an optimal technique, these findings call two prior observations into question. Under dosing at the anterior base region may be overestimated because of poor definition of the prostate-bladder muscle interface. The swelling observed after implantation was lower on T2-weighted images as well, suggesting that a fraction of postimplant swelling is a function of the imaging modality. These findings have implications for preimplant planning and postimplant evaluation. As implant planning techniques become more conformal, and registration methods become more efficient, T2-weighted MRI after implantation will improve the accuracy of postimplant dosimetry.

Prostate position late in the course of external beam therapy: patterns and predictors.

PURPOSE: To examine prostate and seminal vesicles position late in the course of radiation therapy and to determine the effect and predictive value of the bladder and rectum on prostate and seminal vesicles positioning. METHODS AND MATERIALS: Twenty-four patients with localized prostate cancer underwent a computerized tomography scan (CT1) before the start of radiation therapy. After 4-5 weeks of radiation therapy, a second CT scan (CT2) was obtained. All patients were scanned in the supine treatment position with instructions to maintain a full bladder. The prostate, seminal vesicles, bladder, and rectum were contoured. CT2 was aligned via fixed bony anatomy to CT1. The geometrical center and volume of each structure were obtained and directly compared. RESULTS: The prostate shifted along a diagonal axis extending from an anterior-superior position to a posterior-inferior position. The dominant shift was to a more posterior-inferior position. On average, bladder and rectal volumes decreased to 51% (+/-29%) and 82% (+/-45%) of their pretreatment values, respectively. Multiple regression analysis (MRA) revealed that bladder movement and volume change and upper rectum movement were independently associated with prostate motion (p = 0.016, p = 0. 003, and p = 0.052 respectively). CONCLUSION: Patients are often instructed to maintain a full bladder during a course of external beam radiation therapy, in the hopes of decreasing bladder and small bowel toxicity. However, our study shows that large bladder volumes late in therapy are strongly associated with posterior prostate displacement. This prostate displacement may result in marginal miss.

Permanent implantation of 125I sources in the prostate: radical limits of simplicity.

PURPOSE: To determine the effect of reducing the number of sources per implantation on the dose coverage of the prostate volume. MATERIALS AND METHODS: Idealized source distributions were planned for four, eight, 16, 24, 32, and 48 sources. The peripheral loading technique was used to plan a uniform, conformal dose distribution to the target volume, which was the prostate volume as visualized at ultrasonography. Source-placement error was estimated by using measured error magnitudes and was expressed with systematic and random components. The relative sensitivities of the plans to the source-placement error were studied. RESULTS: Idealized planned target coverage can be adequately achieved with comparable dose distributions with eight or more sources. The sensitivity to source-placement error is comparable for plans with 16 or more sources. CONCLUSION: It is theoretically possible to radically simplify implantation without compromising target coverage or error tolerance.

Comparison of multiple bolus and continuous injections of 131I-labeled CC49 for therapy in a colon cancer xenograft model.

One of the problems in achieving cures with radioimmunotherapy is that hematological toxicity limits the quantity of radiolabeled monoclonal antibody (MAb) that can be administered. The MAb CC49 binds with high affinity to the TAG-72 antigen expressed in many human adenocarcinomas. We investigated tumor growth inhibition, survival, and tumor and bone marrow dosimetry after multiple bolus injections or continuous infusion of 131I-labeled CC49 MAb in a human colon cancer xenograft model to determine which method of administration results in the highest therapeutic ratio. Groups of athymic nude mice bearing established s.c. LS174T human colon cancer xenografts received three i.p. bolus injections (3X) of 131I-labeled CC49 (3X, days 0, 3, and 7) or were implanted i.p. with mini-osmotic pumps delivering 131I-labeled CC49 over 7 days. The total radionuclide doses administered were broken down into low-dose (< or = 450 microCi), medium-dose (450-800 microCi), and high-dose (> 800 microCi) groups. At the medium-dose level, the bolus-therapy animals did not have a significantly longer survival time but did have a significantly longer time-to-tumor doubling than the pump-therapy animals. The median survival for medium-dose bolus and pump therapy was 157 and 105 days, respectively, and the median time-to-tumor doubling was at least 114 and 77 days, respectively. At the low-dose level, the bolus-therapy animals had a significantly longer survival time but not a significantly longer time-to-tumor doubling than the pump-therapy animals. The median survival for low-dose bolus and pump therapy was 95.5 and 59 days, respectively, and the median time-to-tumor doubling was 73 and 38 days, respectively. The high-bolus dose was toxic. A comparison of the overall survival rate of pump therapy versus bolus therapy, excluding high-dose, resulted in the bolus-therapy animals having a longer survival time and a longer time-to-tumor doubling than the pump-therapy animals. Serial section autoradiography was used to reconstruct tumor activity density distributions over time. Average dose values calculated from total uptake data for 900 microCi administered activity yielded 158 Gy (3X) and 141 Gy (pump). Average three-dimensional doses using the radial histograms to calculate the absorbed fractions were 139 Gy and 123 Gy, respectively. This calculation includes energy loss external to the tumor. With cell proliferation parameters set to single fraction 60Co recurrence results, the effective dose (D(eff)) for local control was 11 Gy and 9 Gy, respectively. Three bolus injections resulted in a more uniform dose rate over a longer period, resulting in a calculated 19% improvement in D(eff) compared with pump administration. Dose to bone marrow was calculated assuming an activity concentration in bone marrow of 0.24 times the concentration in blood and an absorbed fraction of 0.63. For the 900-microCi 131I-labeled CC49 injected activity, pump administration resulted in an 80% higher calculated D(eff) to bone marrow compared with 3X bolus injection. These results demonstrate that 3X bolus injections were clearly superior to pump administration in terms of survival, tumor growth inhibition, tumor absorbed dose, and bone marrow dose.

A mouse bone marrow dosimetry model.

UNLABELLED: Bone marrow is the primary dose-limiting organ in radioimmunotherapy. Athymic nude mouse models are used to guide radioimmunotherapy in humans. In the mouse, the dimensions of the marrow are comparable to the mean range of the beta particles for a wide variety of beta-emitting radionuclides, so local beta energy deposition cannot be assumed. METHODS: We have developed a computer simulation model in which slab, spherical and cylindrical geometries of the bone marrow of the mouse were incorporated. The energy deposition within the marrow was estimated using beta dose point kernels for several beta-emitting radionuclides. RESULTS: The calculated percentages of energy deposited in the mouse marrow using the full geometry were 46%, 24% and 10% for 131I-, 186Re- and 90Y-radiolabeled antibodies, respectively. Assuming a concentration of activity in the marrow of 0.36 times the blood activity concentration, the percentages of energy deposition in the marrow from marrow and whole-body sources were 61%, 40% and 29% for 131I, 186Re and 90Y, respectively. CONCLUSION: This work shows that, even for the lower mean beta energy-emitting radionuclide, such as 131I, accurate computation of the mouse bone marrow dose involves including both the energy loss from beta decays within the marrow and dose contributions from tissue surrounding the marrow.

Dosimetric comparison of bolus and continuous injections of CC49 monoclonal antibody in a colon cancer xenograft model.

BACKGROUND: Improved understanding of dose and effective dose calculations may contribute to the optimization of fractionated radioimmunotherapy. METHODS: Comparison three-dimensional tumor dosimetry was performed on athymic nude mice bearing established LS174T human colon carcinoma xenografts. Mice were given bolus intraperitoneal injections of 300 microCi 131I-labeled CC49 monoclonal antibody once (Day 0) or three times (Days 0, 3, and 7) or continuous intraperitoneal infusion with miniosmotic pumps over 7 days. Serial section autoradiography was used to reconstruct tumor activity density distributions for Days 3, 4, 7, 10, and 11 (single injection); Days 3, 4, 7, 8, and 11 (3 injections); and Days 4, 7, 10, and 13 (pump). At least three tumors were reconstructed at each time point. Uptakes in blood and tumor were measured up to 14 days (single injection), 11 days (3 injections), or 16 days (pump) after injection. RESULTS: Average dose values calculated from total activity uptake data only (assuming no energy loss external to the tumor) yielded 102 Gy (single injection), 158 Gy (three injections), and 47 Gy (pump). Average doses using three-dimensional dose calculations were 88 Gy, 139 Gy, and 40 Gy, respectively. The nonuniformity of dose deposition affects treatment outcome, because cell loss is an exponential function of dose. Using the linear quadratic model with fractional cell survival to define an effective dose, D(eff) were calculated to be 20 Gy, 23 Gy, and 14 Gy, respectively. Cell proliferation affects outcome for variable dose-rate treatments. With cell proliferation parameters set to reproduce single-fraction 60Co recurrence results, D(eff) (for local control endpoint) were 8.9 Gy, 12.8 Gy, and 3.9 Gy, respectively. Three bolus injections compared with a single bolus injection were relatively less efficient in tumor uptake. However, three bolus injections resulted in a more uniform dose rate over a longer period, resulting in a 50% improvement in D(eff). The slower dose delivery for pump infusion resulted in a significantly lower D(eff), although dose-rate distributions were more uniform compared with the single bolus injection. CONCLUSIONS: Improvement in dose-rate nonuniformities was observed for fractionated and continuous radiolabeled monoclonal antibody injections. Fractionated injections produced superior dosimetric results compared with single bolus or continuous injections.

Impact of ultrasound and computed tomography prostate volume registration on evaluation of permanent prostate implants.

PURPOSE: Ultrasound (US)-guided permanent prostate implants typically use US prostate volumes to plan the implant procedure and CT prostate volumes for 3D dosimetric evaluation of the implant. Such a protocol requires that CT and US prostate volumes be registered. We have studied the impact of prostate volume registration on postimplant dosimetry for patients with low-grade prostate cancer treated with combined US and fluoroscopic-guided permanent implants. METHODS AND MATERIALS: A US image set was obtained with the patient in the lithotomy position to delineate the prostate volume that was subsequently used for treatment planning. Each plan was customized and optimized to ensure complete coverage of the US prostate volume. After implant, a CT scan was obtained for postimplant dosimetry with the patient lying supine. Sources were localized on CT by interactively creating orthogonal images of small cubes, whose dimensions were slightly larger than the source, to assure unique identification of each seed. Ultrasound and CT 3D surfaces were registered using either (a) the rectal surface and base of the prostate, or (b) the Foley balloon and urethra as the alignment reference. A dose distribution was assigned to the US prostate volume based on the CT source distribution, and the dose-volume histogram (DVH) was calculated. RESULT: Prostate volumes drawn from US images differ from those drawn from CT images with the CT volumes being typically larger than the US volumes. Urethral registration of the prostate volume based on aligning the prostatic urethra generates a dose distribution that best follows the preimplant plan and is geometrically the preferable choice for dosimetry. CONCLUSION: The dose distribution and the DVH for the US prostate is sensitive to the mode of registration limiting the ability to determine if acceptable dose coverage has been achieved.

Impact of differences in ultrasound and computed tomography volumes on treatment planning of permanent prostate implants.

PURPOSE: Both ultrasound (US) and computerized tomography (CT) images have been used in the planning of prostate interstitial therapy. Ultrasound images more clearly define the apex and capsule of the prostate, while CT images define seed positions for postimplant dosimetry. Proper registration of the US volume with the CT volume is critical to the assessment of dosimetry. We therefore compared US and CT prostate volumes to determine if differences were significant. METHODS AND MATERIALS: Ten consecutive patients entered in an interstitial implant program were studied by pretreatment US. In addition, pretreatment CT scans were obtained and three physicians independently outlined the dimensions of the prostate on these images. The patients subsequently underwent placement of radioactive 125I or 103Pd. Postimplant CT images were obtained the next day and the postimplant prostate volumes were outlined by the same three physicians. Seven of 10 patients underwent late CT scans 9-14 months postimplant for comparison of preimplant and immediate postimplant CT studies. RESULTS: There were differences between US and CT volumes. Although the physician-to-physician variation was significant, the trends were consistent, with US prostate volume typically smaller (47%) than the preimplant CT volume and markedly smaller (120%) than the postimplant CT volume. Prostate volumes derived from late CT images did not consistently return to preimplant levels. CONCLUSIONS: Significant differences in volume of the prostate structure were found between US and CT images. The data suggests that: (a) Implants planned on CT tend to overestimate the size of the prostate and may lead to unnecessary implantation of the urogenital diaphragm and penile urethra. (b) Registration of initial US and postimplant CT prostate volumes required for accurate dosimetry is difficult due to the increased volume of prostate secondary to trauma. (c) Further study to determine the optimal time for the postimplant CT is necessary.

Source placement error for permanent implant of the prostate.

The performance of ultrasound (US) and fluoroscopic-guided permanent 125I source implant of the prostate using CT identification of the source positions has been evaluated. Marker seeds were implanted during the planning study to assist in the alignment of the US and CT prostate volumes for treatment planning and to guide the placement of needles. The relative positions of the needles and marker seeds were checked by fluoroscopy. A postimplant CT study was used to input the radioactive source positions and to register the sources relative to the preimplant CT and US prostate volumes and the planned source distribution. Source placement errors observed were categorized as: (1) source-to-source spacing differences; (2) needle placement error, both depth and position; and (3) seed splaying, particularly near the prostate periphery. Errors due to source splaying and spacing were in part attributed to prostate motion. Later refinements included fixed-spaced string sources, for which placement errors were smaller than for unattached sources. However, source placement errors due to needle placement error and prostate motion remained unchanged.

Optimal placement of radioisotopes for permanent prostate implants.

PURPOSE: To determine which of four loading techniques most efficiently yields the prescribed dose to the prostate volume while limiting dose to the central urethral volume. MATERIALS AND METHODS: The four techniques included (a) equal activity and equal spacing with nomogram, (b) differential loading, (c) peripheral loading, and (d) spiked loading of the lobes. They were evaluated with regard to target coverage urethra dose, tolerance to error, and complexity of procedure. RESULTS: All ideal plans delivered the prescribed dose of 160 Gy to 99% of the prostate volume. With prostate-volume expansion and source-placement errors, all strategies indicated that at least 71% of the target volume received the prescribed dose and greater than 92% of the target volume received 120 Gy. CONCLUSION: With source-placement errors and glandular swelling, peripheral loading yields the best target coverage while limiting dose to the central urethral volume.

A quantitative study of radionuclide characteristics for radioimmunotherapy from 3D reconstructions using serial autoradiography.

PURPOSE: Using 131I-labeled monoclonal antibody (MoAb) data, assess the dosimetrical impact of labeling the same MoAb with 186Re or 90Y, under the assumption that the biodistribution of the radiolabeled MoAb in tumor relative to blood is independent of the radionuclide. METHODS AND MATERIALS: Radial radioactivity and dose-rate distributions at 1, 4, and 7 days postinjection were derived from three dimensional (3D) reconstructions of serial autoradiographs of LS174T human colon cancer xenografts in athymic nude mice treated with a single intraperitoneal administration of 300 microCi 131I-labeled MoAb 17-1A. Bone marrow dose was calculated taking into account energy deposited external to the bone marrow cavity due to the range of the beta particles. RESULTS: For 1 cm diameter tumors, uptake was mostly at the tumor surface for earlier postinjection times, but exhibited comparable activity levels from the surface to the core of the 7-day sample. The computed dose-rate distributions for 186Re and 90Y were more uniform than for 131I, but smaller fractions of the dose were deposited within the tumor volume due to the larger mean energies of 90Y and 186Re beta particles relative to those for 131I. However, when the tumor doses were normalized to the production of equivalent bone marrow doses, in the case of athymic nude mice, the tumor doses were calculated to be 15.3 Gy (131I), 14.1 Gy (186Re), and 12.0 Gy (90Y). For comparison, these calculations were extended to the case of human therapy, yielding tumor doses of 16.7 Gy (131I), 18.2 Gy (186Re), and 13.4 Gy (90Y). CONCLUSION: In the case of colon cancer xenografts where the MoAb uptake is initially concentrated at the tumor surface, we find a decreasing tumor dose per constant bone marrow dose for radionuclides of increasing mean beta energies and decreasing half-lives. However, a radionuclide with larger mean beta energy such as 90Y generates a significantly more uniform dose deposition within the tumor, especially concerning the core of the tumor, compared to 131I. For human therapy, a gamma component adds little to the tumor dose but increases dose to the marrow.

Reconciliation of tumor dose response to external beam radiotherapy versus radioimmunotherapy with 131iodine-labeled antibody for a colon cancer model.

Reported doses of external beam radiotherapy and radioimmunotherapy (RIT) to produce equivalent therapeutic effects are inconsistent, with many proposed causes. Calculations of effective dose were performed for the case of LS174T human colon cancer xenografts, where a 60Co single fraction exposure (6 Gy) was matched with 131I-labeled 17-1A monoclonal antibody therapy (300 microCi injection, 19 +/- 2 Gy using the Medical Internal Radiation Dose uniform isotropic model). Measured three-dimensional dose-rate distributions were used to form a time-dependent description of the dose-rate nonuniformity. Included in the calculation of RIT effective dose was energy loss, dose nonuniformity, dose-rate dependence, hypoxic fraction, and cell proliferation. The calculations assumed the linear quadratic model for cell survival with alpha = 0.3 Gy-1, alpha/beta = 15 to 25 Gy, and mu = 0.46 h-1. The biologically effective dose for the single fraction 60Co exposure was 7.4 to 8.4 Gy. Estimates of dose efficiency factors consecutively applied to the RIT dose estimate were: (a) energy loss external to the tumor (x0.85); (b) effect of dose nonuniformity on cell survival (x0.65); and (c) effect of correlation of dose nonuniformity with cell proliferation rate (x1.08). The resulting effective dose for RIT was 11.4 Gy for tumor regrowth. This analysis substantially reconciles external beam radiotherapy/RIT dose-response results for this tumor model to within experimental uncertainties.

Three-dimensional reconstruction of monoclonal antibody uptake in tumor and calculation of beta dose-rate nonuniformity.

BACKGROUND: The measurement of the heterogeneity of radiolabeled monoclonal antibody uptake in tumor has an essential role in the calculation and interpretation of the absorbed dose of radiation. Large data arrays and long calculation times have been limiting factors in the calculation of three-dimensional dose-rate distributions used to study the relationship between uptake heterogeneity and dose. METHODS: Serial autoradiographs of tumor sections were digitized with approximately 100 microns resolution using a laser densitometer. The section images were aligned to form a registered tumor-image data set. The image data were corrected for film response versus activity density to create a three dimensional activity density distribution using features of a three-dimensional radiotherapy treatment planning system. Dose-rate distributions were formed by convolution with a beta dose kernel using fast Fourier transforms. RESULTS: Differential dose-rate-volume histograms (derived from the dose-rate distribution) were created to summarize the dose-rate nonuniformity throughout the tumor volume. Effects of section sampling interval, interpolation methods between section planes, and calculation resolution on the dose-rate-volume histograms were illustrated. CONCLUSIONS: The several orders of magnitude improvement in calculational speed provided by the fast Fourier transform technique allowed an investigation of the effects of the calculational parameters. This investigation enabled tuning of both data acquisition and dose computation. These studies can lead to further enhancements in the calculational efficiency of three-dimensional dose-rate distributions. These improvements will allow the study of summing techniques to yield average total dose distributions.

Tissue depth to lung for electron beam boost therapy of the breast.

Radiation therapy of the breast frequently employs electron beam boost therapy of the tumor bed. The electron energy is typically chosen based on the location of the tumor and tissue depth to lung within the electron field. This paper proposes a simple technique to estimate the tissue depth to lung using a port film taken orthogonal to the electron beam axis and patient axis for arbitrary electron beam gantry angles and patient table angles. The port film is taken with the patient in standard position (table angle of 0 degrees) and the gantry at right angles to the electron field axis, clearly showing the depth to lung. The mathematical solution for arbitrary electron field gantry angle and patient table angle is presented.

Multicellular dosimetry for beta-emitting radionuclides: autoradiography, thermoluminescent dosimetry and three-dimensional dose calculations.

Inhomogeneities in activity distributions over distances from 10 to 10(4) microns are observed in many tumors treated with radiolabeled antibodies. Resulting nonuniformities in absorbed dose may have consequences for the efficacy of radioimmunotherapy. Activity variations may be directly studied with quantitative autoradiography (ARG). Converting these data to absorbed dose distributions requires additional information about pharmacokinetics, the use of a point source function and consideration of the complete three-dimensional activity distribution, as obtained from sequential autoradiographic slices. Thermoluminescent dosimetry with specially prepared CaSO4:Dy dosimeters implanted into tissue can directly measure absorbed dose in selected regions. The conditions under which thermoluminescent dosimeters (TLD) are used differ markedly from "normal" use conditions in external beam radiotherapy. Therefore special calibration and quality assurance precautions are needed to assure the precision of this technique. Procedures and pitfalls in the use of both techniques in radioimmunotherapy are described.

Comparison of 131I- and 90Y-labeled monoclonal antibody 17-1A for treatment of human colon cancer xenografts.

The choice of radionuclide remains an important question in clinical radioimmunotherapy. Therefore, a study was initiated, using an in vivo model system, to assess the relative merits of 131I- and 90Y-labeled 17-1A monoclonal antibody as therapeutic agents in the treatment of colon cancer. 131Iodine- and 90Y-labeled 17-1A were assessed in animal therapy trials using athymic nude mice bearing LS174T human colon cancer xenografts. 131Iodine-labeled 17-1A decreased tumor growth in a dose-dependent fashion without lethality. In contrast, the doses of 90Y-labeled 17-1A which were required to produce a significant increase in tumor doubling time also caused marked toxicity. Although similar tumor growth inhibition was produced by 250 microCi 90Y- and 150 microCi 131I-labeled 17-1A, Medical Internal Radiation Dose calculations based on biodistribution data estimated that the dose delivered by 90Y was greater than that delivered by 131I. To investigate this discrepancy, 3-dimensional dose distributions within LS174T tumors were assessed using autoradiography and 3-dimensional calculational techniques. It was found that a greater fraction of the dose was deposited in the tumor after treatment with 131I- compared to 90Y-labeled 17-1A. When the Medical Internal Radiation Dose calculations were adjusted using the 3-dimensional dose distributions, 250 microCi of 90Y- and 150 microCi of 131I-labeled 17-1A were found to deliver similar tumor doses. These studies suggest that 131I-labeled 17-1A is superior to 90Y-labeled 17-1A, since 131I-labeled antibody produced less hematological and animal toxicity and was more effective at inhibiting LS174T tumor growth than 90Y-labeled antibody across the range of radionuclide doses tested. Furthermore, they suggest that it will be necessary to perform 3-dimensional dose calculations in addition to Medical Internal Radiation Dose calculations in order to interpret tumor dosimetry.

Three-dimensional tumor dosimetry for hepatic yttrium-90-microsphere therapy.

The nonuniformity of dose deposition for hepatic 90Y-microsphere therapy is believed to play an important role in the relative sparing of normal liver tissues. To help study this issue, three-dimensional dose calculations have been performed for the VX2 tumor model in the rabbit treated with hepatic arterial administration of 90Y-glass microspheres (90Y-MS). Colored, nonactivated spheres of similar size to 90Y-MS were injected into the hepatic artery to mimic the treatment deposition of 90Y-MS. Sample blocks of treated liver were serially sectioned (200 microns thickness), fixed and photographed showing the position of the colored microspheres. The microsphere positions were digitized into a three-dimensional treatment planning system, and three-dimensional dose calculations were performed. A 2-mm diameter liver tumor nodule receiving 15 times more microspheres than nearby normal liver resulted in tumor-to-normal-tissue (TNT) calculated dose ratios of 2.6 (average dose) and 1.9 (minimum dose). The nonuniform microsphere distribution resulted in a dose gradient over the nodule with a minimum value which was less than one half the average dose. The relative dose deposition in the vicinity of the tumor nodule does not fully reconcile the known liver tolerance dose derived from uniform irradiation with the large calculated average doses tolerated with this type of therapy.