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 ((90)Y) 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 (90)Y PET quantification and evaluates the accuracy of tumor (99m)Tc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry. METHODS: Retrospective dose quantification of (90)Y 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 (90)Y 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 (90)Y PET. RESULTS: Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D(70) > 100 Gy (D(70), minimum dose to 70% tumor volume), whereas incomplete responses were generally at D(70) < 100 Gy; smaller tumors (<80 cm(3)) achieved D(70) > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D(70) 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D(70) 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 (V(20) 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 (90)Y 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 (90)Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor (99m)Tc MAA SPECT/CT predictive dosimetry is feasible. (90)Y DVHs may guide future techniques in predictive dosimetry.