Monte Carlo evaluation of object shape effects in iodine-131 SPET tumor activity quantification.

In our clinical iodine-131 single-photon emission tomography (SPET) quantification for radioimmunotherapy, calibration and partial volume correction are based on measurements with phantoms containing spheres to simulate patient tumors even though real tumors are frequently nonspherical. In this study, Monte Carlo simulation was used to evaluate how object shape influences "spill-out" and "spill-in", which are major sources of quantification error associated with the poor spatial resolution of 131I SPET. Objects that varied in shape (spheres, cylinders, and an irregular structure) but were identical in activity and volume were simulated. Iterative reconstruction employed both attenuation and triple-energy-window scatter compensation. VOIs were defined in the reconstructed images both using physical boundaries and using expanded boundaries to allow for the limited resolution. When physical boundaries were used, both spill-out and spill-in were more significant for nonspherical structures than for spherical structures. Over the range of object volumes (50-200 ml) and at all background levels, VOI counts in cylinders were lower than VOI counts in spheres. This underestimation increased with decrease in object size (for the cold background -18% at 200 ml and -39% at 50 ml). It also decreased with increase in background activity because spill-in partially compensated for spill-out. It was shown that with a VOI larger than physical size, the results are independent of object shape and size only in the case of cold background. Activity quantification was carried out using a procedure similar to that used in our clinic. Quantification of nonspherical objects was improved by simple sphere-based partial volume correction, but the error was still large in some cases (for example, -39% for a 50-ml cylinder in a cold background and -35% for a 200-ml irregular structure defined on the basis of a typical tumor outlined on an X-ray computed tomography scan of a patient with non-Hodgkin's lymphoma). Partial volume correction by patient-specific Monte Carlo simulation may provide better quantification accuracy.

Accuracy of 131I tumor quantification in radioimmunotherapy using SPECT imaging with an ultra-high-energy collimator: Monte Carlo study.

UNLABELLED: Accuracy of 131I tumor quantification after radioimmunotherapy (RIT) was investigated for SPECT imaging with an ultra-high-energy (UHE) collimator designed for imaging 511-keV photons. METHODS: First, measurements and Monte Carlo simulations were carried out to compare the UHE collimator with a conventionally used, high-energy collimator. On the basis of this comparison, the UHE collimator was selected for this investigation, which was carried out by simulation of spherical tumors in a phantom. Reconstruction was by an expectation-maximization algorithm that included scatter and attenuation correction. Keeping the tumor activity constant, simulations were carried out to assess how volume-of-interest (VOI) counts vary with background activity, radius of rotation (ROR), tumor location, and size. The constant calibration factor for quantification was determined from VOI counts corresponding to a 3.63-cm-radius sphere of known activity. Tight VOIs corresponding to the physical size of the spheres or tumors were used. RESULTS: Use of the UHE collimator resulted in a large reduction in 131I penetration, which is especially significant in RIT where background uptake is high. With the UHE collimator, typical patient images showed an improvement in contrast. Considering the desired geometric events, sensitivity was reduced, but only by a factor of 1.6. Simulation results for a 3.63-cm-radius tumor showed that VOI counts vary with background, location, and ROR by less than 3.2%, 3%, and 5.3%, respectively. The variation with tumor size was more significant and was a function of the background. Good quantification accuracy (<6.5% error) was achieved when tumor size was the same as the sphere size used in the calibration, irrespective of the other parameters. For smaller tumors, activities were underestimated by up to -15% for the 2.88-cm-radius sphere, -23% for the 2.29-cm-radius sphere, and -47% for the 1.68-cm-radius sphere. CONCLUSION: Reasonable accuracy can be achieved for VOI quantification of 131I using SPECT with an UHE collimator and a constant calibration factor. Difference in tumor size relative to the size of the calibration sphere had the biggest effect on accuracy, and recovery coefficients are needed to improve quantification of small tumors.

Tumor-absorbed-dose estimates versus response in tositumomab therapy of previously untreated patients with follicular non-Hodgkin's lymphoma: preliminary report.

I-131-radiolabeled tositumomab (Anti-B1 Antibody), in conjunction with unlabeled tositumomab, was employed in a phase II clinical trial for the therapy of 76 previously-untreated follicular-non-Hodgkin's-lymphoma patients at the University of Michigan Cancer Center. For all patients, conjugate-view images were obtained at six to eight time points on seven consecutive days after a tracer infusion of the antibody. A SPECT image set was obtained on day two or three after the therapy infusion for 57 of the patients. Of these, 55 are suitable for dosimetric evaluation. To date, we have completed analysis and response characterization of 20 patients from the subset of 55. All 20 patients had either a complete response (CR) or a partial response (PR). Conjugate-views provided a time-activity curve for a composite of nearby, individual tumors. These tumors were unresolved in the anterior-posterior projection. Pre-therapy CT provided volume estimates. Therapy radiation dose was computed for the composite tumor by standard MIRD methods. Intra-therapy SPECT allowed the calculation of a separate dose estimate for each individual tumor associated with the composite tumor. Average dose estimates for each patient were also calculated. The 30 individual tumors in PR patients had a mean radiation dose of (369 +/- 54) cGy, while the 56 individual tumors in CR patients had a mean radiation dose of (720 +/- 80) cGy. According to a mixed ANOVA analysis, there was a trend toward a significant difference between the radiation dose absorbed by individual tumors for PR patients and that for CR patients. When the radiation dose depended on only the patient response, the p value was 0.04. When the radiation dose depended on the pre-therapy volume of the individual tumor as well as on the patient response, the p value was 0.06. Since the patient response was complete in 75% of the patients, the analysis of the total cohort of 55 evaluable patients is needed to have a larger number of PR patients to better test the trend toward a significant difference. A pseudo-prediction analysis for patient-level dose and response was also carried out. The positive predictive value and the negative predictive value were 73% and 80%, respectively when a patient's average radiation dose was used. The predictive values were 73% and 60%, respectively, when the patient's average base-10 logarithm of radiation dose was used. A complete overlap for the dose range of CR patients compared to that for PR patients precluded higher predictive values. In conclusion, there was a trend toward a significant difference in the radiation dose between CR and PR patients, but it was only moderately predictive of response.

Initial results for Hybrid SPECT--conjugate-view tumor dosimetry in 131I-anti-B1 antibody therapy of previously untreated patients with lymphoma.

UNLABELLED: A study of the use of 131I-labeled anti-B1 monoclonal antibody, proceeded by an unlabeled predose, for therapy of previously untreated non-Hodgkin's lymphoma patients has recently been completed at the University of Michigan, Ann Arbor. More than half of the patients treated were imaged intratherapy with SPECT to separate apparently large tumors, unresolved by conjugate views, into individual ones specified by CT scan. The dosimetry of these tumors is reported here. METHODS: The activity-quantification procedure used 3-dimensional CT-to-SPECT fusion so that attenuation maps could be computed from CT and that volumes of interest could be drawn on the CT slices and transferred to the SPECT images. Daily conjugate-view images after a tracer dose of labeled anti-B1 antibody followed by an unlabeled predose provided the shape of the time-activity curve for the calculation of therapy dosimetry. Reconstructed SPECT counts that were within a volume of interest were converted to activity by using a background-and-radius-adaptive conversion factor. Activities were increased for tumors less than 200 g using a recovery-coefficient factor derived from activity measurements for a set of spheres with volumes ranging from 1.6 to 200 cm3. The calculated tumor radiation absorbed dose was based, in part, on the CT volume and on the intratherapy-SPECT activity. RESULTS: The mean of the radiation dose values for 131 abdominal or pelvic tumors in 31 patients was 616 cGy with a standard deviation of +/- 50 cGy. The largest dose was 40 Gy and the smallest dose was 73 cGy. The mean volume for the tumors was 59.2 +/- 11.2 cm3. The correlation coefficient between absorbed dose and tumor volume was small (r2 = 0.007), and the slope of the least-squares fit represented a decrease of only 36.4 cGy per 100 cm3 increase in volume. This small slope may reflect a characteristic of anti-B1 antibody therapy that is important for its success. The mean absorbed dose per unit administered activity was 1.83 +/- 0.145 Gy/GBq. The largest value was 12.6 Gy/GBq, and the smallest value was 0.149 Gy/GBq. The mean dose for 9 axillary tumors in 5 patients was significantly lower than the average dose for abdominal and pelvic tumors (P = 0.01). Therefore, axillary tumors should be grouped separately in assessing dose-response relationships. Anecdotal patient results tended to verify the validity of using the shape of the conjugate-view time-activity curve for the average SPECT-intratherapy curve. However, there was also an indication that the shape varies somewhat for individual tumors with respect to time to peak. CONCLUSION: Hybrid SPECT-conjugate-view dosimetry provided radiation absorbed dose estimates for the individual patient tumors that were resolved by CT.

Characterization of scatter and penetration using Monte Carlo simulation in 131I imaging.

UNLABELLED: In 131I SPECT, image quality and quantification accuracy are degraded by object scatter as well as scatter and penetration in the collimator. The characterization of energy and spatial distributions of scatter and penetration performed in this study by Monte Carlo simulation will be useful for the development and evaluation of techniques that compensate for such events in 131I imaging. METHODS: First, to test the accuracy of the Monte Carlo model, simulated and measured data were compared for both a point source and a phantom. Next, simulations to investigate scatter and penetration were performed for four geometries: point source in air, point source in a water-filled cylinder, hot sphere in a cylinder filled with nonradioactive water, and hot sphere in a cylinder filled with radioactive water. Energy spectra were separated according to order of scatter, type of interaction, and gamma-ray emission energy. A preliminary evaluation of the triple-energy window (TEW) scatter correction method was performed. RESULTS: The accuracy of the Monte Carlo model was verified by the good agreement between measured and simulated energy spectra and radial point spread functions. For a point source in air, simulations show that 73% of events in the photopeak window had either scattered in or penetrated the collimator, indicating the significance of collimator interactions. For a point source in a water-filled phantom, the separated energy spectra showed that a 20% photopeak window can be used to eliminate events that scatter more than two times in the phantom. For the hot sphere phantoms, it was shown that in the photopeak region the spectrum shape of penetration events is very similar to that of primary (no scatter and no penetration) events. For the hot sphere regions of interest, the percentage difference between true scatter counts and the TEW estimate of scatter counts was <12%. CONCLUSION: In 131I SPECT, object scatter as well as collimator scatter and penetration are significant. The TEW method provides a reasonable correction for scatter, but the similarity between the 364-keV primary and penetration energy spectra makes it difficult to compensate for these penetration events using techniques that are based on spectral analysis.

I-131 anti-B1 therapy/tracer uptake ratio using a new procedure for fusion of tracer images to computed tomography images.

In patients with non-Hodgkin's lymphoma being treated by I-131-radiolabeled anti-B1 monoclonal antibody, we test the hypothesis that the activity taken up in tumors during therapy is the same as that observed during tracer evaluation, except for scaling by the ratio of administered activities. Chemotherapy-relapsed patients are imaged only with planar conjugate views, whereas previously untreated patients are imaged with planar conjugate views and with single-photon emission computed tomography (SPECT). The SPECT tracer activity quantification requires computed tomography (CT) to SPECT image fusion, for which we devised a new procedure: first, the tracer SPECT images are fused to the therapy SPECT images. Then, that transformation is combined with the therapy SPECT-to-CT transformation. We also use (a) the same volumes of interest defined on CT for both tracer and therapy image sets, and (b) a SPECT counts-to-activity conversion factor that adapts to background and rotation radius. We define R as the ratio of therapy activity percentage of infused dose over tracer activity percentage of infused dose at 2-3 days after monoclonal antibody infusion. For 31 chemotherapy-relapsed patients, the R ratio for 60 solitary or composite tumors averages 0.931 +/- 0.031. The hypothesis of R being 1 is rejected with greater than 95% confidence. However, the difference from 1 is only 7.4%. The range of R is 0.43-1.55. For seven previously untreated patients, R averages 1.050 +/- 0.050 for 24 solitary tumors evaluated by SPECT. For six of these patients, R averages 0.946 +/- 0.098 for one of these solitary tumors and for five composite tumors, evaluated by conjugate views. Both results agree with the hypothesis that R is 1. The range of R for the SPECT tumors is 0.71 +/- 0.03 to 1.82 +/- 0.53, and for the conjugate view tumors, it is 0.70-1.35. Plots of R versus tumor volume yield small correlation coefficients. That from SPECT approaches a statistically significant difference from zero correlation (P = 0.06). In summary, on average, the tumor percentage of infused dose following tracer administration is predictive of therapeutic percentage of infused dose within 8%. For greater accuracy with individual tumors, however, an intratherapy evaluation is probably necessary because the range of R is large.

MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates.

This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates.

Deadtime correction for two multihead Anger cameras in 131I dual-energy-window-acquisition mode.

Two side-by-side energy windows, one at the photopeak and one at lower energy, are sometimes employed in quantitative SPECT studies. We measured the count-rate losses at moderately high activities of 131I for two multihead Anger cameras in such a dual-window-acquisition mode by imaging a decaying source composed of two hot spheres within a warm cylinder successively over a total of 23 days. The window locations were kept fixed and the paralyzable model was assumed. In addition, for the Picker Prism 3000 XP camera, the source was viewed from three different angles separated by 120 degrees and the final results are from an average over these three angles. For the Picker camera, the fits to the data from the individual windows are good (the mean of the squared correlation coefficient equals 0.98) while for the Siemens Multispect camera fits to the data from head 1 and from the lower-energy, monitor window are relatively poor. Therefore, with the Siemens camera the data from the two windows are combined for deadtime computation. Repeated autopeaking might improve the fits. At the maximum count rate, corresponding to a total activity of 740 MBq (20 mCi) in the phantom, the multiplicative deadtime correction factor is considerably larger for the Picker than for the Siemens camera. For the Picker camera, it is 1.11, 1.12, and 1.12 for heads 1-3 with the photopeak window and 1.10 for all heads with the lower-energy monitor window. For the Siemens camera, the combined-window deadtime correction factor is 1.02 for head 1 and 1.03 for head 2. Differences between the deadtime correction factor for focal activity and for the total activity do not support the hypothesis of count misplacement between foci of activity at these count rates. Therefore, the total-image dead time correction is recommended for any and all parts of the image.

Preliminary results from intensity-based CT-SPECT fusion in I-131 anti-B1 monoclonal-antibody therapy of lymphoma.

BACKGROUND: In treatment of non-Hodgkin's lymphoma patients with predose-plus-I-131-labeled anti-B1 (anti-CD20) monoclonal antibody, an intratherapy single photon emission computed tomography (SPECT) image is an important part of research estimates of tumor dosimetry. For that imaging, a computed tomography (CT)-SPECT fusion is used both to obtain an attenuation map for the space-alternating generalized expectation maximization reconstruction and to provide CT-based volumes of interest (VoI) to determine activity in tumors and organs. Fusion based on external, skin-surface markers has been used but may not correctly superimpose internal structures. METHODS: A new algorithm, developed and implemented in the Department of Radiology, University of Michigan, and based on the mutual information of grayscale values, was investigated. Results from four anti-B1 therapy patients are presented. RESULTS: In one patient, the new intensity-based fusion provided total reconstructed counts for kidneys that were higher than those produced by marker-based fusion; therefore, the VoI was probably located more accurately. In a second patient, after an acquisition that did not include any skin markers, the new algorithm produced counts/pixel that were similar for four of five tumors consistent with what is expected from an ideal therapy combined with accurate count density estimates. The fifth tumor was quite small and will have its final activity estimate moved toward consistency with the others after a recovery coefficient multiplication. For four tumors in two patients, direct comparison of the two algorithms yielded count totals that were different by no more than 7.2%. CONCLUSIONS: The use of CT-SPECT fusion and subsequent transfer of tumor VoI originally drawn in high-resolution CT space offers potential advantages for quantifying tumor uptake of radioactivity. A new, mutual-information-based fusion algorithm is usable without skin markers. Results indicate that the new fusion algorithm gives equal tumor count values within 7.2% compared with fusion based on external markers. It increases estimates of kidney activity by an average of 6.4%.

A Monte Carlo investigation of dual-energy-window scatter correction for volume-of-interest quantification in 99Tcm SPECT.

Using Monte Carlo simulation of 99Tcm single-photon-emission computed tomography (SPECT), we investigate the effects of tissue-background activity, tumour location, patient size, uncertainty of energy windows, and definition of tumour region on the accuracy of quantification. The dual-energy-window method of correction for Compton scattering is employed and the multiplier which yields correct activity for the VI as a whole calculated. The model is usually a sphere containing radioactive water located within a cylinder filled with a more dilute solution of radioactivity. Two simulation codes are employed. Reconstruction is by ML-EM algorithm with attenuation compensation. The scatter multiplier depends only slightly on the sphere location or the cylinder diameter. It also depends little on whether correction is before or after reconstruction. At low background level, it changes with VOI size, but not at higher background. For a geometrical VOI, it is 1.25 at zero background, decreases sharply to 0.56 for equal concentrations, and is 0.44 when the background concentration is very large. Quantification is accurate (less than 9% error) if the test background is reasonably close to that used in setting the universal scatter-multiplier value, or if the test backgrounds are always large and so is the universal-value background, but not if the test backgrounds cover a large range of values including zero. Results largely agree with those from experiment after the experimental data with background is re-evaluated with prejudice.

CT-SPECT fusion plus conjugate views for determining dosimetry in iodine-131-monoclonal antibody therapy of lymphoma patients.

UNLABELLED: A method for performing 131I quantitative SPECT imaging is described which uses the superimposition of markers placed on the skin to accomplish fusion of computed tomography (CT) and SPECT image sets. METHODS: To calculate mean absorbed dose after administration of one of two 131I-labeled monoclonal antibodies (Mabs), the shape of the time-activity curve is measured by daily diagnostic conjugate views, the y-axis of that curve is normalized by a quantitative SPECT measurement (usually intra-therapy), and the tumor mass is deduced from a concurrent CT volume measurement. The method is applied to six B-cell non-Hodgkin's lymphoma patients. RESULTS: For four tumors in three patients treated with the MB1 Mab, a correlation appears to be present between resulting mean absorbed dose and disease response. Including all dosimetric estimates for both antibodies, the range for the specific absorbed dose is within that found by others in treating B-cell lymphoma patients. Excluding a retreated anti-B1 patient, the tumor-specific absorbed dose during anti-B1 therapy is from 1.4 to 1.7 mGy/MBq. For the one anti-B1 patient, where quantitative SPECT and conjugate-view imaging was carried out back to back, the quantitative SPECT-measured activity was somewhat less for the spleen and much less for the tumor than that from conjugate views. CONCLUSION: The quantitative SPECT plus conjugate views method may be of general utility for macro-dosimetry of 131I therapies.

Autoradiography-based, three-dimensional calculation of dose rate for murine, human-tumor xenografts.

A Fast Fourier Transform method for calculating the three-dimensional dose rate distribution for murine, human-tumor xenografts is outlined. The required input includes evenly-spaced activity slices which span the tumor. Numerical values in these slices are determined by quantitative 125I autoradiography. For the absorbed dose-rate calculation, we assume the activity from both 131I- and 90Y-labeled radiopharmaceuticals would be distributed as is measured with the 125I label. Two example cases are presented: an ovarian-carcinoma xenograft with an IgG 2ak monoclonal antibody and a neuroblastoma xenograft with meta-iodobenzylguanidine (MIBG). Considering all the volume elements in a tumor, we show, by comparison of histograms and also relative standard deviations, that the measured 125I activity and the calculated 131I dose-rate distributions, are similarly non-uniform and that they are more non-uniform than the calculated 90Y dose-rate distribution. However, the maximum-to-minimum ratio, another measure of non-uniformity, decreases by roughly an order of magnitude from one distribution to the next in the order given above.

Dead time of an anger camera in dual-energy-window-acquisition mode.

Two side-by-side energy windows are sometimes employed in quantitative single photon emission computed tomography (SPECT) studies. The count-rate losses at high activities for a GE400AT camera were measured in such a dual-window-acquisition mode by imaging a decaying source composed of a hot sphere within a warm cylinder. The data in each window was either kept separate or combined for purposes of dead-time correction and the paralyzable model was assumed. In addition, correction factors were derived from a "monitor" source at the edge of the camera. Finally, energy spectra for only the monitor-source region of interest and for the entire camera were obtained under both low- and high-count conditions and compared. With 99mTc (1) the spectral measurements show no peak shift but reveal pulse-pile-up spectral degradation. (2) The monitor-source corrections do not agree well with those from the model, presumably because of the differential effects of such degradation. For this camera the preferred correction method for patients is one using the model and two, effective, phantom-derived dead times for the separate data from the two windows. The two effective dead times are needed to compensate for pulse pile-up adding more counts to the lower-energy window than to the higher-energy one at high rates.(ABSTRACT TRUNCATED AT 250 WORDS)

An overview of imaging techniques and physical aspects of treatment planning in radioimmunotherapy.

Planar and tomographic imaging techniques and methods of treatment planning in clinical radioimmunotherapy are reviewed. In clinical trials, the data needed for dosimetry and treatment planning are, in most cases, obtained from noninvasive imaging procedures. The required data include tumor and normal organ volumes, the activity of radiolabeled antibodies taken up in these volumes, and the pharmacokinetics of the administered activity of radiolabeled antibodies. Therefore, the topics addressed in this review include: (1) Volume determination of tumors and normal organs from x-ray-computed tomography and magnetic resonance imaging, (2) quantitation of the activity of radiolabeled antibodies in tumors and normal organs from planar gamma camera views, (3) quantitative single-photon emission computed tomography and positron emission tomography, (4) correlative image analysis, and (5) treatment planning in clinical radioimmunotherapy.

Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma.

PURPOSE: This study was undertaken to evaluate the tumor targeting, toxicity, and therapeutic potential of the anti-B-cell-reactive monoclonal antibody MB-1 (anti-CD37) labeled with iodine 131 given in a nonmarrow ablative dose range in B-cell lymphoma patients who relapsed after chemotherapy. PATIENTS AND METHODS: Twelve patients with MB-1-reactive tumors were infused first with 40 mg of trace-labeled (3 to 7 mCi) MB-1. Ten patients who had no serious toxicity postinfusion and who had successful tumor imaging on serial gamma scans then received at least one 40-mg radioimmunotherapy (RIT) dose (25 to 161 mCi). Tracer estimates of delivered whole-body dose (WBD) were used in prescribing a millicurie RIT dose for seven patients. RESULTS: Eleven patients had positive tumor imaging after a tracer dose, including patients with bulky tumors and/or large tumor burdens (> or = 1 kg) +/- splenomegaly. However, overall sensitivity for the detection of known tumor sites was only 39%. In six of eight patients with dose-assessable tumors, the radiation dose to at least one tumor was 1.1 to 3.1 times higher than to any normal organ, excluding the spleen for a 40-mg tracer dose. Tracer-dose toxicities included reversible glossal edema in one patient, grade 3 hepatic transaminasemia in another, and early drops in both circulating B and T cells (with decreases in B cells more pronounced) in nearly all patients. RIT toxicity was primarily myelosuppression (especially thrombocytopenia), which had a delayed onset and protracted recovery (without significant recovery until at least 2 months post-RIT). Grade 3 myelosuppression in two of two patients who were treated at a tracer-projected 50-cGy WBD level (133 and 149 mCi) precluded further planned RIT dose escalation. Less myelosuppression was generally observed in patients who were treated at < or = 40-cGy WBD levels. Antimouse antibodies developed in two patients. Six patients had tumor responses post-RIT. Four had responses that lasted more than 1 month (2 to 6 months), which included one complete response, one partial response, one minor response, and one mixed response. Responses seemed to occur more frequently in imaged tumors than in nonimaged tumors. The most durable response occurred in a patient who had the best antibody targeting to tumor. CONCLUSIONS: Although 131I-MB-1 has limited diagnostic value, it can produce tumor responses at nonmarrow ablative RIT doses. Further studies that focus on improving tumor targeting with this or other B-cell-reactive radiolabeled antibodies and on ameliorating the myelosuppression associated with the RIT-dosing approach used in this trial are warranted.

A regularized deconvolution-fitting method for Compton-scatter correction in SPECT.

A method is presented for estimating the Compton-scatter component within the photopeak for local energy spectra measured by an Anger camera in SPECT. Assuming that the measured energy spectrum is the source scatter energy distribution convolved with a known camera energy-resolution function plus an unscattered spectral component, a least-square inverse operation is performed to recover the source scatter distribution. Since this inverse operation is ill-posed, the regularization technique is applied for stabilization. With the method, scatter fractions similar to those from polynomial spectral fitting (PSF) have been observed for experimentally measured, high-count data with a hot (Tc(99m) or I(131)) sphere in a cold cylinder, and the inverse (Tc(99m) only). The method is also less sensitive to the width of the fitting window. A regularization parameter from 1 to 10 is recommended for practical cases. The shape of a recovered source scatter distribution matches that determined by a high-resolution semiconductor-detector measurement as well as by Monte Carlo simulation.

Quantitative autoradiographic evaluation of the influence of protein dose on monoclonal antibody distribution in human ovarian adenocarcinoma xenografts.

We studied the effect of monoclonal antibody protein dose on the uniformity of radioiodinated antibody distribution within tumor masses using quantitative autoradiography. Groups (n = 11-13/group) of athymic nude mice with subcutaneous HTB77 human ovarian carcinoma xenografts were injected intraperitoneally with an 125I-labeled anticarcinoma-associated antigen murine monoclonal antibody, 5G6.4 using a high or a low protein dose (500 micrograms or 5 micrograms). At 6 days post-injection the macroscopic and microscopic intratumoral biodistribution of radiolabeled antibody was determined. The degree of heterogeneity of the labeled antibody distribution within each tumor was quantified and expressed as the coefficient of variation (CV) of the activity levels in serial histological sections. Tumors from mice given the 500-micrograms protein doses had substantially lower CV values, 0.327 +/- 0.027, than did tumors from animals given 5-micrograms protein doses, 0.458 +/- 0.041, (P = 0.0078), indicating that the higher protein dose resulted in more homogeneous distribution of radioactivity in tumors than did the lower dose. While the percentage of the injected dose reaching the tumor was comparable between groups, injecting the higher dose of protein resulted in significantly lower tumor to non-tumor uptake ratios than those obtained for the lower protein dose. These data indicate, in this system, that to achieve more uniform intratumoral antibody (and radiation for radioimmunotherapy) delivery, a relatively high protein dose must be administered. However, to obtain this increased uniformity, a substantial drop in tumor/background uptake ratios was seen. Quantitative autoradiographic evaluation of human tumor xenografts is a useful method to assess the intratumoral distribution of antibodies.