Dose Calculations and Dose-Effect Relationships in 177Lu-PSMA I&T Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer

Abstract

Introduction Dose response of 22 patients experiencing mCRPC (metastatic castration-resistant prostate cancer) to 177Lu-PSMA I&T radionuclide therapy was investigated. Dosimetry calculations are used to assess correlations between dosimetric quantities and biomarker values. Methods The patients’ age range was 74 ± 7 years at the time of the investigated treatment cycle, and the mean injected activity was 7416 ± 218 MBq. Planar images at several time points postinjection were used for evaluation of absorbed doses to organs and lesion. 68Ga-PSMA PET/CT follow-up imaging enabled the determination of individual tumor molecular volume (TMV) shrinkage. Changes in 7 different biomarkers after the first treatment cycle were correlated with the calculated absorbed organ and TMV doses, resulting in a total number of 259 investigated correlations. Results Sixty-three TMVs were identified in the bone, lymph node, and liver tissue with an average reduction of 32.3%, 84.7%, and 72.9%, respectively. Absorbed doses per unit of administered activity for organs and lesions show good agreement with previous works (0.77, 0.71, and 0.27 mGy/MBq for parotid gland, kidneys, and liver as well as 4.38, 5.47, and 4.95 mGy/MBq for bone, lymph node, and liver malignancies, respectively). Only 37 of 259 possible correlations turned out to be statistically significant, 26 of which are associated with the absorbed dose of an organ and the decrease of alkaline phosphatases. Conclusions Although treatment with 177Lu-PSMA I&T leads to a big reduction of TMV in patients with mCRPC, the lack of correlations calls for studies using voxel-wise dosimetry based on SPECT/CTs.

Streamlined Schemes for Dosimetry of 177Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

“…Dosimetry enables the estimation of doses to organs at risk (OAR) and tumor lesions which are known to show high intra-and inter-patient and intra-lesion variability due to different factors such as receptor density, binding affinity and tumor volume. In addition to legal regulations, individual assessment of doses to OAR is mandatory for a patient-specific approach in PSMA-RLT and might allow for the administration of higher cumulative activities, thereby increasing doses to the tumor and hence improving response to therapy significantly as recently shown by several studies [8][9][10][11][12]. Additionally, this position is supported by the EANM Guideline for PSMA-targeted therapies [13].…”

Clinical implementation of PLANET® Dose for dosimetric assessment after [177Lu]Lu-DOTA-TATE: comparison with Dosimetry Toolkit® and OLINDA/EXM® V1.0

“…GE Healthcare recommends to use a procedure based on planar acquisition to determine the calibration factor (CF; in counts.s −1 .MBq −1 ). For clinical dosimetry, different [19] scenarios are available: whole-body, hybrid, or multi-SPECT/CT image acquisition. It includes two steps.…”

Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

“…However, this treated cohort represents the patient population referred to PSMA-RLT in clinical routine quite well. Additionally, although we have previously published part of our dosimetric data in a subgroup of patients who obtained the first PSMA-RLT course [26], the lack of such information in this current study could limit its outcomes. The reason lies in the crucial role of radiation dosimetry in estimating the therapy response and level of absorbed radiation dose, not only for each individual metastasis but also for the organs physiologically exhibiting an uptake of PSMA-RLT [27] and thereby evaluating their degree of therapy toxicity [28].…”