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.

Comparison of fatty acid tracers FTHA and BMIPP during myocardial ischemia and hypoxia.

UNLABELLED: To study the sensitivity of two fatty acid tracers to changes in beta-oxidation, the myocardial retention kinetics of 125I-iodine-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) and 14-18F-fluoro-6-thia-heptadecanoic acid (FTHA) were compared in states of oxygen deprivation due to ischemia and hypoxia. METHODS: Nineteen swine were studied by extracorporeal perfusion of the three coronary arteries. Fatty acid beta-oxidation rates were determined by infusion of tritiated palmitate into the left anterior descending artery (LAD) and by measurement of labeled water production in the LAD perfusion bed. After a baseline period of 30 min, animals were divided into three groups and subjected to a 50-min intervention period. For the control group, there was no change in perfusion; for the ischemia group, there was a 60% decrease in LAD perfusion; and for the hypoxia group, the perfusion rate was unchanged, but venous blood was used as the LAD perfusate. Continuous infusion of FTHA and BMIPP into the LAD started 10 min into the intervention period and continued until the end of the intervention period. Retention rates of the two tracers were compared between the LAD and circumflex perfusion beds. RESULTS: No difference in beta-oxidation rate occurred from the baseline to the intervention period in the control group. A 50% reduction in beta-oxidation occurred in the ischemia group, and an 80% reduction occurred in the hypoxia group. No difference in retention of BMIPP or FTHA occurred in the control group. In the ischemia group, reduction in retention of both tracers occurred. However, in the hypoxia group, FTHA uptake was unchanged, whereas BMIPP retention increased compared to the circumflex arterial bed. CONCLUSION: Decreased retention of both BMIPP and FTHA occurred with ischemia, despite the known differences in metabolism of the two tracers. This difference in metabolism was further highlighted in the setting of hypoxia with increased BMIPP uptake. Thus, these results suggest that uptake of both FTHA and BMIPP tracks reduction of fatty acid utilization in myocardial ischemia but fails in tracking reduction of fatty acid oxidation during hypoxia.

Metabolic response of non-Hodgkin's lymphoma to 131I-anti-B1 radioimmunotherapy: evaluation with FDG PET.

UNLABELLED: 131I-anti-B1 (CD20) radioimmunotherapy (RIT) is a promising approach for treatment of non-Hodgkin's lymphoma (NHL). We assessed the tumor metabolic response to RIT using FDG PET. METHODS: We examined 14 patients with NHL, who were given first a tracer dose of 131I-anti-B1 and then RIT, each preceded by infusion of unlabeled anti-B1. In 8 of 14 patients, PET was performed at baseline and 33-70 d after RIT. The other 6 patients underwent PET at baseline, 6-7 d after the tracer dose, and 5-7 d after RIT to estimate the early response to tracer dose and RIT. To assess tumor FDG uptake, standardized uptake value normalized for lean body mass (SUV-lean) was measured 1 h after FDG injection. RESULTS: After RIT, complete response was observed in 6 patients, partial response in 6, and no response in 2. At 33-70 d after RIT, mean SUV-lean of 6 responders markedly declined to 41% of the baseline value (P < 0.002). Soon after tracer dose and after RIT, mean SUV-lean of the other 6 responders decreased to 79% and 62% of the baseline values, respectively (P < 0.05). In 2 nonresponders, SUV-lean did not significantly decline from the baseline value at 37 d after RIT. CONCLUSION: FDG PET metabolic data obtained 1-2 mo after RIT correlate well with the ultimate best response of NHL to RIT, more significantly than the early data after tracer dose or RIT. FDG uptake in NHL may decline gradually after RIT in responding patients.

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.

Attenuation characteristics of a new compensator material: Thermo-Shield for high energy electron and photon beams.

A new thermoplastic material with extremely desirable physical and radiation shielding properties is presented. The material softens between 108 degrees F and 132 degrees F and can then be easily molded to any desired shape. As it cools down it hardens at about 102 degrees F, retaining its molded shape. It is very light (rho = 1.66 g/cc), compared to most other compensating and shielding materials used in the clinic. Its photon and electron attenuation characteristics have been measured and are compared with other materials relevant to radiotherapy. Possible applications as a bolus material, compensator and partial or total shielding material in clinical radiation therapy are discussed.

Affinities of dopamine analogs for monoamine granular and plasma membrane transporters: implications for PET dopamine studies.

Affinities of dopamine (DA) analogs to both granular and plasma membrane uptake transporters were measured in vitro by inhibition of [3H]DA uptake in bovine chromaffin granule ghosts and C6 glial cells transfected with cDNA for the rat presynaptic dopamine transporter, respectively. Five amines were studied: DA, 6-fluorodopamine (6FDA), m-tyramine (MTA), 6-fluoro-m-tyramine (6FMTA), and beta-fluoromethylene-m-tyramine (FMMTA). Direct uptake of 18F labeled 6FDA and 6FMTA was also measured in the chromaffin granule system and compared with [3H]DA uptake. Results show that the transporter affinities of 6FDA and MTA were similar to that of DA in both transport systems while affinities of 6FMTA and FMMTA were lower. Furthermore while the direct uptake of DA and FDA in chromaffin granules were essentially identical and significantly reserpine-inhibitable, the direct uptake of 6FMTA was about 15-fold less and only minimally sensitive to reserpine pretreatment. Thus, although vesicular protection and reuptake may influence the turnover of FDA in 6-fluoroDOPA studies, they are unlikely to be important determinants of the kinetics of the slowly clearing components in studies with either 6-fluoro-m-tyrosine (6FMT) or 6-fluoro-beta-fluoro-methylene-m-tyrosine (6FFMMT), the bioprecursors of 6FMTA and 6-fluoro-FMMTA, respectively. These results are consistent with the finding that the longterm component in 6FMT PET studies is 6-fluoro-hydroxyphenylacetic acid (6FHPAC), which can be explained by the lack of vesicular protection of 6FMTA from MAO oxidation.

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.