Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

Purpose: To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. Methods: This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Results: Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. Conclusions: During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

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.

Dosimetry in patients with B-cell lymphoma treated with [(90)Y]ibritumomab tiuxetan or [(131)I]tositumomab.

Radioimmunotherapy involves the use of radiolabeled monoclonal antibodies (MAbs) to treat malignancy. The therapeutic effect is determined by the radiopharmaceutical, the radiation absorbed dose and previous treatments. There are currently two approved radiopharmaceuticals for the treatment of B-cell lymphoma - the (90)Y-labeled ibritumomab and the (131)I-labeled tositumomab. Both are directed against CD20, albeit not against the same epitope. This paper summarizes current results of dose-responses for normal tissues and tumours of [(131)I]tositumomab and [(90)Y]ibritumomab tiuxetan, discusses them in the context of dosimetry methods used and highlights the assumptions being made in the different dosimetry methodologies. Moreover, we wish to point at the possibility of performing low-cost therapy bremsstrahlung imaging for [(90)Y]ibritumomab tiuxetan to confirm biodistribution, and possibly also for dosimetric calculations.

Method for Fast CT/SPECT-Based 3D Monte Carlo Absorbed Dose Computations in Internal Emitter Therapy.

The DPM (Dose Planning Method) Monte Carlo electron and photon transport program, designed for fast computation of radiation absorbed dose in external beam radiotherapy, has been adapted to the calculation of absorbed dose in patient-specific internal emitter therapy. Because both its photon and electron transport mechanics algorithms have been optimized for fast computation in 3D voxelized geometries (in particular, those derived from CT scans), DPM is perfectly suited for performing patient-specific absorbed dose calculations in internal emitter therapy. In the updated version of DPM developed for the current work, the necessary inputs are a patient CT image, a registered SPECT image, and any number of registered masks defining regions of interest. DPM has been benchmarked for internal emitter therapy applications by comparing computed absorption fractions for a variety of organs using a Zubal phantom with reference results from the Medical Internal Radionuclide Dose (MIRD) Committee standards. In addition, the ß decay source algorithm and the photon tracking algorithm of DPM have been further benchmarked by comparison to experimental data. This paper presents a description of the program, the results of the benchmark studies, and some sample computations using patient data from radioimmunotherapy studies using (131)I.

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.