Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma

Aim In vivo pharmacokinetic analysis of [Sc-44]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu-177]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu-177]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Methods Pharmacokinetics of [Sc-44]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc-44. Afterward, forward decay correction using the half-life of Lu-177 was performed, extrapolating the pharmacokinetics of [Sc-44]Sc-PSMA-617 to that of [Lu-177]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu-177]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu-177]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. Results The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). Conclusions [Sc-44]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc-44]Sc-PSMA-617 to that of [Lu-177]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu-177]Lu-PSMA-617.