Endocrine Abstracts

Aim: It is common practice to administer peptide receptor radionuclide therapy (PRRT) at fixed injected activity (IA) per cycle. This results in highly variable radiation doses to critical organs and undertreatment of most patients. We conceived a personalized PRRT (P-PRRT) system enabling delivery of a prescribed dose to the kidney over four cycles. Our goal was to assess the potential of P-PRRT to safely increase radiation dose rate to tumors, by performing a simulation in a retrospective cohort.

Methods: Twenty-two patients underwent a four-cycle, empiric-IA induction course of ¹⁷⁷Lu-octreotate PRRT (29.6±2.4 GBq cumulative IA), with quantitative SPECT/CT-based dosimetry. Kidney, bone marrow (BM) and maximum tumor doses were 16.2±5.5, 1.3±0.8 and 114±66 Gy, respectively. We simulated P-PRRT, in which the renal dose per IA is predicted by the body surface area and glomerular filtration rate for the first cycle, and by prior cycle(s)’ dosimetry data for subsequent cycles. Personalized IA is determined at each cycle, in order to reach the prescribed renal dose of 23 Gy over four cycles (25–50% reduction if impaired renal or BM function). Simulated IAs and doses were based on actual patients’ characteristics, lab values and doses per IA delivered at each of the 88 cycles.

Results: P-PRRT would have allowed increasing cumulative IA to 43.7±16.5 GBq over four cycles, which would have increased kidney, BM and maximum tumor doses to 21.5±2.5, 1.6±0.6 and 156±82 Gy, respectively. There was an average 1.45-fold increase of tumor dose over empiric PRRT (range: 0.68–2.34 folds; P=0.0025).

Conclusion: By standardizing the dose rate to the kidney instead of the IA per cycle, P-PRRT offers the prospect of significantly increasing tumor radiation doses, and thus the likelihood of therapeutic benefits, while limiting the risk of toxicity. We are currently evaluating this approach in a registered prospective trial.