90Y-DOTATOC Dosimetry-Based Personalized Peptide Receptor Radionuclide Therapy

Abstract

Pretherapy PET with ⁸⁶Y-DOTATOC is considered the ideal dosimetry protocol for ⁹⁰Y-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 ⁹⁰Y-DOTATOC using ⁹⁰Y-DOTATOC PET/CT and bremsstrahlung SPECT/CT and to determine whether dosimetry-based administered activities differ significantly from standard administered activities. Methods: This was a prospective phase 2 trial of ⁹⁰Y-DOTATOC therapy in patients with somatostatin receptor-positive tumors. ⁹⁰Y-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/m²; 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 ⁹⁰Y-DOTATOC PET/CT at 5 h after therapy and ⁹⁰Y-DOTATOC bremsstrahlung SPECT/CT at 6, 24, 48, and 72 h. The PET/CT data were used to measure the absolute concentration of ⁹⁰Y-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 ⁹⁰Y-DOTATOC) with the energy emitted per decay, divided by the mass of the kidneys. Results: The radiation dose to the kidneys per cycle of ⁹⁰Y-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 ⁹⁰Y-DOTATOC, the administered activity was modified by at least 20% from the starting administered activity. Conclusion: Renal dosimetry of ⁹⁰Y-DOTATOC is feasible using ⁹⁰Y-DOTATOC time-of-flight PET/CT and bremsstrahlung SPECT/CT and has a significant impact on the administered activity in treatment cycles.

Keywords: 90Y-DOTATOC; dosimetry; neuroendocrine; peptide receptor radiotherapy; radiobiology/dosimetry; radionuclide therapy.

FIGURE 1.

Typical biexponential curve of renal clearance of ⁹⁰Y-DOTATOC, with initial fast elimination followed by slow clearance.

FIGURE 2.

Distribution of renal absorbed doses from 47 administrations of ⁹⁰Y-DOTATOC.

FIGURE 3.

Distribution of bone marrow doses from 47 administrations of ⁹⁰Y-DOTATOC.

FIGURE 4.

Distribution of administered activity per cycle for each subject.