Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome.

While [177Lu]Lu-PSMA radioligand therapy is currently only applied in end-stage metastatic castrate-resistant prostate cancer (mCRPC) patients, also low-volume hormone-sensitive metastatic prostate cancer (mHSPC) patients can benefit from it. However, there are toxicity concerns related to the sink effect in low-volume disease. This prospective study aims to determine the kinetics of [177Lu]Lu-PSMA in mHSPC patients, analyzing the doses to organs at risk (salivary glands, kidneys, liver, and bone marrow) and tumor lesions < 1 cm diameter.

Ten mHSPC patients underwent two cycles of [177Lu]Lu-PSMA therapy. Three-bed position SPECT/CT was performed at 5 time points after each therapy. Organ dosimetry and lesion dosimetry were performed using commercial software and a manual approach, respectively. Correlation between absorbed index lesion dose and treatment response (PSA drop of > 50% at the end of the study) was calculated and given as Spearman's r and p-values.

Kinetics of [177Lu]Lu-PSMA in mHSPC patients are comparable to those in mCRPC patients. Lesion absorbed dose was high (3.25 ± 3.19 Gy/GBq) compared to organ absorbed dose (salivary glands: 0.39 ± 0.17 Gy/GBq, kidneys: 0.49 ± 0.11 Gy/GBq, liver: 0.09 ± 0.01 Gy/GBq, bone marrow: 0.017 ± 0.008 Gy/GBq). A statistically significant correlation was found between treatment response and absorbed index lesion dose (p = 0.047).

We successfully performed small lesion dosimetry and showed that the tumor sink effect in mHSPC patients is of less concern than was expected. Tumor-to-organ ratio of absorbed dose was high and tumor uptake correlates with PSA response. Additional treatment cycles are legitimate in terms of organ toxicity and could lead to better tumor response.

European journal of nuclear medicine and molecular imaging. 2021 Jul 04 [Epub ahead of print]

Steffie M B Peters, Bastiaan M Privé, Maarten de Bakker, Frank de Lange, Walter Jentzen, Annemarie Eek, Constantijn H J Muselaers, Niven Mehra, J Alfred Witjes, Martin Gotthardt, James Nagarajah, Mark W Konijnenberg

Department of Medical Imaging, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. ., Department of Medical Imaging, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands., Department of Nuclear Medicine, University of Duisburg-Essen, Essen, Germany., Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.

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