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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 49; no. 2; pp. 460 - 469
• Main Authors: Peters, Steffie M. B., Privé, Bastiaan M., de Bakker, Maarten, de Lange, Frank, Jentzen, Walter, Eek, Annemarie, Muselaers, Constantijn H. J., Mehra, Niven, Witjes, J. Alfred, Gotthardt, Martin, Nagarajah, James, Konijnenberg, Mark W.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-01-2022; Springer Nature B.V
• Subjects: Bone marrow; Bone tumors; Cardiology; Correlation; Dosimeters; Dosimetry; Exocrine glands; Hormones - metabolism; Humans; Imaging; Kidneys; Kinetics; Lesions; Liver; Lutetium - adverse effects; Lutetium - pharmacokinetics; Lutetium - therapeutic use; Lutetium isotopes; Male; Medicine; Medicine & Public Health; Metastases; Metastasis; Nuclear Medicine; Oncology; Organs; Organs at Risk - diagnostic imaging; Organs at Risk - radiation effects; Original; Original Article; Orthopedics; Patients; Prospective Studies; Prostate cancer; Prostate-Specific Antigen - adverse effects; Prostate-Specific Antigen - blood; Prostate-Specific Antigen - pharmacokinetics; Prostate-Specific Antigen - therapeutic use; Prostatic Neoplasms - blood; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - radiotherapy; Prostatic Neoplasms - secondary; Radiation Dosage; Radiology; Radiopharmaceuticals - adverse effects; Radiopharmaceuticals - pharmacokinetics; Radiopharmaceuticals - therapeutic use; Salivary gland; Salivary glands; Single photon emission computed tomography; Single Photon Emission Computed Tomography Computed Tomography; Statistical analysis; Therapy; Toxicity; Treatment Outcome; Tumors; Radionuclide therapy; mHSPC; [; Dosimetry; Prostate cancer; Lu]Lu-PSMA; [177Lu]Lu-PSMA
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-021-05471-4

Introduction
While [
177
Lu]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 [
177
Lu]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 [
177
Lu]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 [
177
Lu]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.