A gelatin liver phantom of suspended 90Y resin microspheres to simulate the physiologic microsphere biodistribution of a postradioembolization liver.

UNLABELLED: For phantom studies involving (90)Y PET/CT, homogeneous solutions of (90)Y, for example, (90)Y citrate, are commonly used. However, the microsphere biodistribution of a postradioembolization liver is never homogeneous; therefore, such phantoms are physiologically unrealistic for simulating clinical scenarios. The aim of this work was to develop a safe and practical phantom capable of simulating the heterogeneous microsphere biodistribution of a postradioembolization liver. METHODS: Gelatin (5%) was used to suspend (90)Y resin microspheres, poured into plastic containers to simulate a liver with 2 tumors. Microspheres were added while the gelatin was maintained in a liquid state on a hot plate and continuously stirred with magnetic stir bars. The liquid microsphere mixture was then rapidly cooled in an ice bath while being stirred, resulting in a heterogeneous suspension of microspheres. The completed phantom was serially scanned by (90)Y PET/CT over 2 wk. RESULTS: All scans demonstrated a heterogeneous microsphere distribution throughout the liver and tumor inserts. Serendipitously, magnetic stir bars left inside the phantom produced CT artifacts similar to those caused by embolization coils, whereas pockets of air trapped within the gelatin during its preparation mimicked gas within hollow viscus. The microspheres and tumor inserts remained fixed and suspended within the gelatin, with no evidence of breakdown or leakage. CONCLUSION: A gelatin phantom realistically simulating the physiologic microsphere biodistribution of a postradioembolization liver is feasible to construct in a radiopharmacy.

Personalized dosimetry of 131I-rituximab radioimmunotherapy of non-hodgkin lymphoma defined by pharmacokinetics in bone marrow and blood.

PURPOSE: To report a comparison of SPECT/CT technique with standard blood-based dosimetry methodology in a cohort of non-Hodgkin lymphoma (NHL) patients treated with 131I-rituximab anti-CD20 chimeric monoclonal antibody. METHODOLOGY: Red marrow uptake was measured directly using serial quantitative whole-body imaging in conjunction with SPECT/CT in a cohort of 23 patients undergoing routine 131I-rituximab radioimmunotherapy of NHL. Absorbed dose measurements were then compared with radiation doses calculated using standard peripheral blood counting methodology. RESULTS: Activity clearance from whole body of 88.7 hours measured by imaging 131I-rituximab was significantly slower (p<0.001) than the mean effective half-life clearance of 60.8 hours calculated from the sampling peripheral blood. The mean activity concentrations in bone marrow measured using SPECT/CT, and by blood sampling, extrapolated to the time of administration, were, however, concordant. The absorbed self-dose in red marrow, measured using imaging, was 1.02 Gy compared with the dose (0.81 Gy) calculated from blood sampling. Neutrophil toxicity correlated with absorbed dose by SPECT/CT imaging (p=0.01), whereas the blood sampling method demonstrated no correlation with any parameters of hematological toxicity. CONCLUSION: Radiation dose to red marrow from 131I-rituximab is inherently underestimated by standard indirect peripheral blood counting methods. Personalized marrow dosimetry by quantitative gamma imaging more accurately predicts of hemopoietic myelotoxicity by direct measurement of the bone marrow activity concentration of 131I-rituximab.

Post-radioembolization yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres.

BACKGROUND: Coincidence imaging of low-abundance yttrium-90 (90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry. METHODS: Retrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET. RESULTS: Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D70 > 100 Gy (D70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D70 < 100 Gy; smaller tumors (<80 cm3) achieved D70 > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy (V20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those by 90Y PET, with a low median relative error of +3.8% (95% confidence interval, -1.2% to +13.2%). CONCLUSIONS: Tumor and non-target tissue absorbed dose quantification by 90Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor 99mTc MAA SPECT/CT predictive dosimetry is feasible. 90Y DVHs may guide future techniques in predictive dosimetry.

Early prediction of response to chemotherapy and survival in malignant pleural mesothelioma using a novel semiautomated 3-dimensional volume-based analysis of serial 18F-FDG PET scans.

UNLABELLED: The aim of chemotherapy for mesothelioma is to palliate symptoms and improve survival. Measuring response using CT is challenging because of the circumferential tumor growth pattern. This study aims to evaluate the role of serial (18)F-FDG PET in the assessment of response to chemotherapy in patients with mesothelioma. METHODS: Patients were prospectively recruited and underwent both (18)F-FDG PET and conventional radiological response assessment before and after 1 cycle of chemotherapy. Quantitative volume-based (18)F-FDG PET analysis was performed to obtain the total glycolytic volume (TGV) of the tumor. Survival outcomes were measured. RESULTS: Twenty-three patients were suitable for both radiological and (18)F-FDG PET analysis, of whom 20 had CT measurable disease. After 1 cycle of chemotherapy, 7 patients attained a partial response and 13 had stable disease on CT assessment by modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria. In the 7 patients with radiological partial response, the median TGV on quantitative PET analysis fell to 30% of baseline (range, 11%-71%). After 1 cycle of chemotherapy, Cox regression analysis demonstrated a statistically significant relationship between a fall in TGV and improved patient survival (P = 0.015). Neither a reduction in the maximum standardized uptake value (P = 0.097) nor CT (P = 0.131) demonstrated a statistically significant association with patient survival. CONCLUSION: Semiquantitative (18)F-FDG PET using the volume-based parameter of TGV is feasible in mesothelioma and may predict response to chemotherapy and patient survival after 1 cycle of treatment. Therefore, metabolic imaging has the potential to improve the care of patients receiving chemotherapy for mesothelioma by the early identification of responding patients. This technology may also be useful in the assessment of new systemic treatments for mesothelioma.

Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in (131)I-anti-CD20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma.

PURPOSE: Radioimmunotherapy (RIT) for relapsed non-Hodgkin's lymphoma is emerging as a promising treatment strategy. Myelosuppression is the dose-limiting toxicity and may be particularly problematic in patients heavily pretreated with chemotherapy. Reliable dosimetry is likely to minimise toxicity and improve treatment efficacy, and the aim of this study was to elucidate the complex problems of dosimetry of RIT by using an integrated SPECT/CT system. METHODS: As a part of a clinical trial of (131)I-anti-CD20 rituximab RIT of non-Hodgkin's lymphoma, we employed a patient-specific prospective dosimetry method utilising the whole-body effective half-life of antibody and the patient's ideal weight to calculate the administered activity for RIT corresponding to a prescribed radiation absorbed dose of 0.75 Gy to the whole body. A novel technique of quantitation of bone marrow uptake with hybrid SPECT/CT imaging was developed to validate this methodology by using post-RIT extended imaging and data collection. RESULTS: A strong, statistically significant correlation (p=0.001) between whole-body effective half-life of antibody and effective marrow half-life was demonstrated. Furthermore, it was found that bone marrow activity concentration was proportional to administered activity per unit weight, height or body surface area (p<0.001). CONCLUSION: The results of this study show the proposed whole-body dosimetry method to be valid and clinically applicable for safe, effective RIT.