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

• DOI: 10.1007/s00259-021-05471-4
• Publication Date: 2021-07-04T09:02:31Z
• Authors: Steffie M. B. Peters; Bastiaan M. Privé; Maarten de Bakker; Frank de Lange; Walter Jentzen; Annemarie Eek; Constantijn H. J....; Niven Mehra; J. Alfred Witjes; Martin Gotthardt; James Nagarajah; Mark W. Konijnenberg
• Keywords: Male; Organs at Risk; Single Photon Emission Computed Tomography Computed Tomography; Radboudumc 15: Urological cancers RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health Sciences; Lutetium; Radiation Dosage; 03 medical and health sciences; 0302 clinical medicine; SDG 3 - Good Health and Well-being; Medical Imaging - Radboud University Medical Center; Humans; Prospective Studies; Medical Oncology - Radboud University Medical Center; Prostatic Neoplasms; Prostate-Specific Antigen; Radboudumc 14: Tumours of the digestive tract RIHS: Radboud Institute for Health Sciences; Hormones; 3. Good health; Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences; Treatment Outcome; Urology - Radboud University Medical Center; Original Article; Radiopharmaceuticals; Radboudumc 0: Other Research RIHS: Radboud Institute for Health Sciences

Abstract Introduction 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.

Methods 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.

Results 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).

Conclusions 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.