Alternative Means of Estimating 131I Maximum Permissible Activity to Treat Thyroid Cancer.

To protect bone marrow from overirradiation, the maximum permissible activity (MPA) of 131I to treat thyroid cancer is that which limits the absorbed dose to blood (as a surrogate of marrow) to less than 200 cGy. The conventional approach (method 1) requires repeated γ-camera whole-body measurements along with blood samples. We sought to determine whether reliable MPA values can be obtained by simplified procedures. Methods: Data acquired over multiple time points were examined retrospectively for 65 thyroid cancer patients, referred to determine 131I uptake and MPA for initial treatment after thyroidectomy (n = 39), including 17 patients with compromised renal function and 22 patients with known (n = 16) or suspected (n = 6) metastases. The total absorbed dose to blood (DTotal) was the sum of mean whole-body γ-ray dose component (Dγ) from uncollimated γ-camera measurements and dose due to ß emissions (Dß) from blood samples. Method 2 estimated DTotal from Dß alone, method 3 estimated DTotal from Dγ alone, and method 4 estimated DTotal from a single 48-h γ-camera measurement. MPA was computed as 200 cGy/DTotal for each DTotal estimate. Results: Method 2 had the strongest correlation with conventional method 1 (r = 0.98) and values similar to method 1 (21.0 ± 13.7 cGy/GBq vs. 21.0 ± 14.1 cGy/GBq, P = 0.11), whereas method 3 had a weaker (P = 0.001) correlation (r = 0.94) and method 4 had the weakest (P < 0.0001) correlation (r = 0.69) and lower dose (16.3 ± 14.8 cGy/GBq, P < 0.0001). Consequently, correlation with method 1 MPA was strongest for method 2 MPA (r = 0.99) and weakest for method 4 (r = 0. 75). Method 2 and method 1 values agreed equally well regardless of whether patients had been treated with 131I previously or had abnormal renal function. Conclusion: Because MPA based on blood measurements alone is comparable to MPA obtained with combined body counting and blood sampling, blood measurements alone are sufficient for determining MPA.

Human Radiation Dosimetry for the N-Methyl-D-Aspartate Receptor Radioligand 11C-CNS5161.

UNLABELLED: (11)C-CNS5161 (N-(2-chloro-5-methylthiophenyl)-N'-(3-methylthiophenyl)-N'-(11)C-methylguanidine) has been successfully used in PET imaging of N-methyl-d-aspartate (NMDA) receptors. However, no human dosimetry data have been published. We are planning to use this radiotracer for investigating NMDA receptor function in systemic lupus erythematosus, traumatic brain injury, and Parkinson disease. We have therefore undertaken (11)C-CNS5161 PET imaging to measure the whole-body distribution of this radionuclide and to estimate radiation dose to various organs. METHODS: Dynamic PET studies of the whole body were performed on 5 healthy adults. Regions of interest were drawn over the visualized structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations. S factors were implemented within the OLINDA/EXM software for each structure or organ. RESULTS: For (11)C-CNS5161, organ doses ranged from 0.0002 to 0.0393 mGy/MBq (0.0006-0.1455 rad/mCi). The critical organ for radiation burden was the lungs, with a dose of 0.0393 mGy/MBq (0.1455 rad/mCi). Radiation doses to the reproductive and blood-forming organs were 0.0023, 0.0002, and 0.0020 mGy/MBq (0.0086, 0.0006, and 0.0074 rad/mCi) for the ovaries, testes, and red marrow, respectively. The effective dose equivalent was 0.0106 mSv/MBq (0.0392 rem/mCi). CONCLUSION: The radiation dosimetry for (11)C-CNS5161 for a standard single injection of 555 MBq (15 mCi) will result in an effective dose equivalent of 5.9 mSv (0.59 rem) and a lung dose of 21.8 mGy (2.18 rad) in young, healthy subjects.

Dosimetry of the dopamine transporter radioligand 18F-FPCIT in human subjects.

UNLABELLED: This study was designed to evaluate the radiation dosimetry in human subjects for a new radiopharmaceutical, N-(3-(18)F-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane ((18)F-FPCIT). The goal was to determine a limiting dose consistent with accepted guidelines for use in clinical studies and to compare the radiation burden with other agents such as (123)I-FPCIT, (18)F-fluorodopa, and (18)F-FDG. METHODS: Dynamic PET scans of the urinary bladder were obtained in 6 subjects; 2 subjects had brain scans and 5 subjects had scans of the thorax or abdomen. Regions of interest were placed over composite images of each organ for which activity was visualized to generate time-activity curves. Doses were calculated from residence times using the MIRDOSE3 program. RESULTS: The critical organ for dosimetry is the urinary bladder wall with a dose of 0.0586 +/- 0.0164 mGy/MBq. The dose comes primarily (97.2%) from activity in the urinary bladder contents. The dose is lower than any of the other agents used commonly in PET to assess dopaminergic function. The effective dose equivalent (0.0120 mGy/MBq) is also lower than comparable compounds. CONCLUSION: (18)F-FPCIT has favorable dosimetry when compared with other agents used to study dopaminergic function. Doses as high as 853 MBq (23 mCi) may be given to adult patients and remain within accepted guidelines.

Outcome and toxicity associated with maximum safe dose radioiodine treatment of metastatic thyroid cancer.

PURPOSE: This study was designed to determine the outcomes of patients referred to the authors' nuclear medicine service for dosimetric evaluation and treatment of metastatic thyroid cancer with radioiodine I-131. In addition, the incidence and severity of hematologic toxicity associated with treatment were determined. METHODS: A retrospective review of patients referred for dosimetric evaluation was undertaken for the years 1984 to 2000. Chart reviews were performed for 20 patients treated with at least 80% of the calculated maximum safe dose. Outcomes were evaluated for 15 patients for whom sufficient follow-up information was available. The incidence and severity of hematologic toxicity were determined for 12 of the 20 patients. RESULTS: Outcomes were defined as good, fair, or poor. One third of the patients had good, one third had fair, and one third had poor outcomes. Three patients experienced anemia, but no life-threatening hematologic toxicity was observed in any of the patients. Serum thyroglobulin measurements proved to be an efficacious way to predict outcome. The use of recombinant human thyrotropin appears to have increased the sensitivity of the thyroglobulin measurements. CONCLUSIONS: Radioiodine I-131 treatments produce variable outcomes in patients with advanced disease. Hematologic toxicity is well controlled in patients if dosimetric guidelines are followed. I-131 treatment appeared to retard the progression of metastatic thyroid cancer in 50% of the patients who were not cured. Radioiodine doses may be increased to improve efficacy without associated irreversible toxicity.

A new method to measure thyroid uptake with a gamma camera without routine use of a standard source.

PURPOSE: This study was designed to validate a reliable gamma camera-based method for measuring thyroid uptake. The method is based on a stable calibration procedure and does not require daily use of a standard source. In addition, the method is designed to overcome deadtime losses inherent in uptake probe measurements with iodine-123. METHODS: A calibration procedure was designed using I-123 capsules in a neck phantom and tested using two gamma cameras. Patient thyroid uptake measurements made with the proposed gamma camera method were correlated with measurements obtained using the traditional uptake probe technique. Image quality was compared between the low-energy, parallel-hole collimator used in this study and the pinhole collimator usually used for thyroid imaging. RESULTS: Capsule count rates measured using the gamma camera are linear with activity, and the calibration procedure is reproducible when tests are performed several months apart. Thyroid uptake measured with the gamma camera correlated closely (R2 > 0.9) with measurements made using the probe technique. Image quality with the low-energy parallel-hole collimator was comparable to that obtained with the pinhole collimator. CONCLUSIONS: The proposed camera-based method for measuring thyroid uptake is accurate and reproducible. It can be performed readily in conjunction with the routine scan procedure. Adoption of this technique reduces equipment requirements in the nuclear medicine department.

Radiation absorbed dose to the basal ganglia from dopamine transporter radioligand 18F-FPCIT.

Our previous dosimetry studies have demonstrated that for dopaminergic radiotracers, (18)F-FDOPA and (18)F-FPCIT, the urinary bladder is the critical organ. As these tracers accumulate in the basal ganglia (BG) with high affinity and long residence times, radiation dose to the BG may become significant, especially in normal control subjects. We have performed dynamic PET measurements using (18)F-FPCIT in 16 normal adult subjects to determine if in fact the BG, although not a whole organ, but a well-defined substructure, receives the highest dose. Regions of interest were drawn over left and right BG structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations. S-factors were computed using the MIRDOSE3 nodule model for each caudate and putamen. For (18)F-FPCIT, BG dose ranged from 0.029 to 0.069 mGy/MBq. In half of all subjects, BG dose exceeded 85% of the published critical organ (bladder) dose, and in three of those, the BG dose exceeded that for the bladder. The BG can become the dose-limiting organ in studies using dopamine transporter ligands. For some normal subjects studied with F-18 or long half-life radionuclide, the BG may exceed bladder dose and become the critical structure.

Quantitative Brain PET. Comparison of 2D and 3D Acquisitions on the GE Advance Scanner.

PURPOSE: Recent developments in the design of positron emission tomography (PET) scanners have made three-dimensional (3D) data acquisition attractive because of significantly higher sensitivity compared to the conventional 2D mode (with lead/tungsten septa extended). However, the increased count rate in 3D mode comes at the cost of increased scatter, randoms, and dead time. Several schemes to correct for these effects have been proposed and validated in phantom studies. In this study, we evaluated the overall improvement afforded by 3D imaging in quantitative human brain PET studies carried out at our institution.METHODS: Subjects were studied using sequential/interleaved 2D and 3D data acquisition with a GE Advance scanner. We calculated regional and global cerebral glucose metabolism with [(18)F]flourodeoxyglucose (FDG) and estimated rate constants for striatal [(18)F]fluorodopa (FDOPA) uptake.RESULTS: FDG: Global mean glucose metabolic rates were in almost complete agreement (within 1%) between the two modes whereas the regional differences ranged from -7.7% to +9% for all cortical structures. However, for small regions (<2 cm(2)) like caudate nuclei, the maximum difference was 14.7%. FDOPA: A significant improvement in image quality was evident in 3D mode and there was complete agreement between the estimated parameters in the two scanning modes for the same noise equivalent counts: Striatal-to-occipital ratio (SOR) and striatal FDOPA uptake (K(i)(FD)) had mean differences of less than 2% and 5%, respectively.CONCLUSIONS: 3D FDG studies can be done with either half the injected dose or half the scan duration to a comparable 2D study. 3D PET imaging has distinct advantages over 2D in the quantitative fluorodopa studies.