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.

Zusammenfassung

Ziel Patienten mit fortgeschrittenem Prostatakrebs sind geeignete Kandidaten für die [¹⁷⁷Lu]-PSMA-617-Therapie. SPECT/CT-Systeme haben das Potenzial, die patientenspezifische Tumordosimetrie zu verbessern. Wir stellen einen neuen patientenspezifischen, Monte-Carlo-basierten voxelweisen Dosimetrieansatz vor, um Organ- und totale Tumordosen (TTD) zu bestimmen.

Methodik 13 Patienten mit histologisch gesichertem metastasiertem kastrationsresistentem Prostatakrebs wurden mit insgesamt 18 Zyklen [¹⁷⁷Lu]-PSMA-617 behandelt. Bei jedem Patienten wurde eine Dosimetrie nach dem ersten Therapiezyklus durchgeführt. Volumes of interest (VOIs) wurden manuell auf den SPECT/CT-Bildern für die Nieren, die Milz und alle 295 PSMA-positiven Tumorläsionen im Untersuchungsgebiet definiert. Die absorbierte Dosis für Organe und alle Tumorläsionen wurden mittels einer 3-dimensionalen Monte-Carlo-basierten Simulation berechnet.

Ergebnisse Die mittleren Dosiswerte wurden wie folgt bestimmt: 2,59 ± 0,63 Gy (1,67–3,92 Gy) für die Nieren, 0,79 ± 0,46 Gy (0,31–1,90 Gy) für die Milz und 11,00 ± 11,97 Gy (1,28–49,10 Gy) für alle Tracer-positiven Tumorläsionen. Ein Trend zu höheren totalen Tumordosen wurde in Patienten mit Gleason-Scores > 8 im Vergleich zu Gleason-Scores ≤ 8 und in Patienten mit Lymphknotenmetastasen im Vergleich zu Knochenmetastasen beobachtet. Eine signifikante Korrelation wurde zwischen Serum-PSA-Werten vor Radioligandentherapie und der totalen Tumordosis ermittelt (r = –0,57; p < 0,05) sowie zwischen der totalen Tumordosis und der prozentualen Änderung der Serum-PSA-Werte vor und nach Therapie beobachtet (r = –0,57; p < 0,05). Patienten mit höherem totalem Tumorvolumen der PSMA-positiven Läsionen zeigten signifikant geringere mittlere Nierendosen (r = –0,58; p < 0,05).

Schlussfolgerung Die vorgestellte neuartige Monte-Carlo-basierte voxelweise Dosimetrie berechnet eine patientenspezifische Ganzkörper-Dosisverteilung, die individuelle Gewebezusammensetzungen berücksichtigt und vielversprechende Resultate für die Bestimmung der absorbierten Dosis von Organen und PSMA-positiven Tumorläsionen zeigt.

Key words

PSMA - dosimetry - prostate cancer - radioligand therapy

Schlüsselwörter

PSMA - Dosimetrie - Prostatakrebs - Radioligandentherapie

Publication History

Received: 17 April 2020

Accepted: 17 June 2020

Article published online:
14 July 2020

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