Y-DOTATOC Dosimetry-Based Personalized Peptide Receptor Radionuclide Therapy.

Pretherapy PET with Y-DOTATOC is considered the ideal dosimetry protocol for Y-DOTATOC therapy; however, its cost, limited availability, and need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. The goal of this study was to develop a dosimetric method for Y-DOTATOC using Y-DOTATOC PET/CT and bremsstrahlung SPECT/CT and to determine whether dosimetry-based administered activities differ significantly from standard administered activities. This was a prospective phase 2 trial of Y-DOTATOC therapy in patients with somatostatin receptor-positive tumors. Y-DOTATOC was given in 3 cycles 6-8 wk apart. In the first cycle of therapy, adults received 4.4 GBq and children received 1.85 GBq/m; the subsequent administered activities were adjusted according to the dosimetry of the preceding cycle so as not to exceed a total kidney dose of 23 Gy and bone marrow dose of 2 Gy. The radiation dose to the kidneys was determined from serial imaging sessions consisting of time-of-flight Y-DOTATOC PET/CT at 5 h after therapy and Y-DOTATOC bremsstrahlung SPECT/CT at 6, 24, 48, and 72 h. The PET/CT data were used to measure the absolute concentration of Y-DOTATOC and to calibrate the bremsstrahlung SPECT kidney clearance data. The radiation dose to the kidneys was determined by multiplying the time-integrated activity (from the fitted biexponential curve of renal clearance of Y-DOTATOC) with the energy emitted per decay, divided by the mass of the kidneys. The radiation dose to the kidneys per cycle of Y-DOTATOC therapy was highly variable among patients, ranging from 0.32 to 3.0 mGy/MBq. In 17 (85%) of the 20 adult patients who received the second and the third treatment cycles of Y-DOTATOC, the administered activity was modified by at least 20% from the starting administered activity. Renal dosimetry of Y-DOTATOC is feasible using Y-DOTATOC time-of-flight PET/CT and bremsstrahlung SPECT/CT and has a significant impact on the administered activity in treatment cycles.