Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received (111)In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8 ) on day 0 followed by a therapeutic dose of 90Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of (111)In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T(1/2), blood AUC, plasma T(1/2), and plasma AUC. It is concluded that 90Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T(1/2), reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population.

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Background:The prostate-specific membrane antigen (PSMA) has been targeted for PET imaging and radioligand therapy (RLT) in patients with prostate cancer. Xerostomia is a common side effect of RLT due to high salivary gland uptake of PSMA-radioligands.Here we aimed to determine the impact of monosodium glutamate (MSG) administration on PSMA-radioligand biodistribution within healthy organs and tumor lesions by using 68 Ga-PSMA-11 PET imaging.Methods: 16 men with prostate cancer were randomized (1:1) into oral ingestion and oral topical application ('swishing') arms. Each subject underwent two 68 Ga-PSMA-11 PET/CT scans within 14 days under baseline and MSG conditions. Salivary glands and wholebody tumor lesions were segmented using qPSMA software. We quantified tracer uptake via mean and maximum standardized uptake values (SUVmean and SUVmax) and compared parameters within each patient.Results: For the oral ingestion arm, salivary gland SUVmean/max decreased on average from Control to MSG scan by 45±15% (p=0.004) and 53±11% (p<0.001), respectively.Tumor lesions SUVmean/ max also decreased by 38% (IQR -67%, -33%) and -52% (IQR -70%, -49%), respectively (p=0.018). Swishing had no significant effect on 68 Ga-PSMA-11 accumulation in normal organs or tumor lesions. Conclusion:Oral ingestion but not topical application of MSG reduced 68 Ga-PSMA-11 uptake in salivary glands. Tumor uptake also declined, therefore, the clinical application of MSG is unlikely to be useful in the framework of RLT.