Estimation of [177Lu]PSMA-617 tumor uptake based on voxel-wise 3D Monte Carlo tumor dosimetry in patients with metastasized castration resistant prostate cancer

Abstract

Objective Patients with advanced prostate cancer are suitable candidates for [177Lu]PSMA-617 therapy. Integrated SPECT/CT systems have the potential to improve the accuracy of patient-specific tumor dosimetry. We present a novel patient-specific Monte Carlo based voxel-wise dosimetry approach to determine organ and total tumor doses (TTD). Methods 13 patients with histologically confirmed metastasized castration-resistant prostate cancer were treated with a total of 18 cycles of [177Lu]PSMA-617 therapy. In each patient, dosimetry was performed after the first cycle of [177Lu]PSMA-617 therapy. Regions of interest were defined manually on the SPECT/CT images for the kidneys, spleen and all 295 PSMA-positive tumor lesions in the field of view. The absorbed dose to normal organs and to all tumor lesions were calculated by a three dimensional dosimetry method based on Monte Carlo Simulations. Results The average dose values yielded the following results: 2.59 ± 0.63 Gy (1.67–3.92 Gy) for the kidneys, 0.79 ± 0.46 Gy (0.31–1.90 Gy) for the spleen and 11.00 ± 11.97 Gy (1.28–49.10 Gy) for all tracer-positive tumor lesions. A trend towards higher TTD was observed in patients with Gleason Scores > 8 compared to Gleason Scores ≤ 8 and in lymph node metastases compared to bone metastases. A significant correlation was determined between the serum-PSA level before RLT and the TTD (r = –0.57, p < 0.05), as well as between the TTD with the percentage change of serum-PSA levels before and after therapy was observed (r = –0.57, p < 0.05). Patients with higher total tumor volumes of PSMA-positive lesions demonstrated significantly lower kidney average dose values (r = –0.58, p < 0.05). Conclusion The presented novel Monte Carlo based voxel-wise dosimetry calculates a patient specific whole-body dose distribution, thus taking into account individual anatomies and tissue compositions showing promising results for the estimation of radiation doses of normal organs and PSMA-positive tumor lesions.

Dual-Time-Point Posttherapy177Lu-PSMA-617 SPECT/CT Describes the Uptake Kinetics of mCRPC Lesions and Prognosticates Patients’ Outcome

“…Existing data on 177 Lu-PSMA-617 RLT dosimetry indicate that the radiation dose delivered to the target is key in ensuring response (21,22). However, in a recent systematic review, a relevant variability in tumor dose (range, 7.5-77.6 Gy) was highlighted across and within populations (23).…”

Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT)

“…Consequently, [ 177 Lu]Lu-PSMA-617 was approved using fixed standard treatment activities, and patient individual dosimetry is not mandatory for in-label use. Comparable dosimetry estimates have also been obtained in several academically driven dosimetry studies covering various in-house formulations of [ 177 Lu]Lu-PSMA-617 (e.g., with different specific activities GBq/mmol) [22,23,31,36,61,70,[87][88][89][90][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122] (Annex Table -5). Similar absorbed doses to organs-at-risk have also been approximated when using [ 177 Lu]Lu-PSMA-I&T [75,81,98,[123][124][125][126] (Annex Table-5).…”

Individuelle Dosimetrie der Nieren bei der Therapie des metastasierten kastrationsresistenten Prostatakarzinoms mit 177Lu-Prostataspezifischem Membranantigen (177Lu-PSMA) mittels konventioneller nuklearmedizinischer Diagnostik

“…eine SPECT/CT-Komponente, mit der eine Korrektur der Schwächung und Streuung möglich war 81,94. Insbesondere bei Violet et al ergaben sich Ergebnisse mit einer hohen Aussagekraft, da mit einer Anzahl von 30 Patienten verhältnismäßig viele Nierendosen ausgewertet wurden.…”