This paper aims to review and critically analyze current nuclear medicine procedures able to assess the treatment response to [177Lu]Lu-PSMA, highlighting their strengths and limitations, as well as future developments.
A comprehensive literature search was made by using PubMed and Scopus databases, until August 2025. The following search strings were employed: A: "prostate cancer" OR "prostate neoplas*" OR "prostate malignan*"; B: "Lutetium" OR "177Lu-PSMA" OR "PSMA therapy" OR "Lutetium-177 PSMA" OR "LuPSMA" OR "177Lu-PSMA-617" OR "177Lu-PSMA-I&T" OR "lutetium-labeled PSMA," C: "treatment response" OR "response assessment" OR "response evaluation" OR "treatment efficacy" OR "therapy outcome" OR "therapeutic response." Only English-language studies were included, but no publication year restrictions were applied, ensuring a broad search strategy. Additionally, the references of included articles were screened to identify further relevant studies.
A total of 23 studies were included in the final analysis, encompassing 1419 patients. Most studies were retrospective (N.=19). [68Ga]Ga-PSMA-11 PET/CT was the most frequently used modality for response assessment, either alone or in combination with [18F]-labelled PSMA ligands. Several studies incorporated [177Lu]Lu-PSMA SPECT/CT, particularly for post-therapy response evaluation. Response assessments were performed after the first or second RLT cycle, whereas the remaining studies extended evaluation to the third or fourth cycle or to end-of-treatment time points. Volumes at SPECT/CT during or at the end of PSMA-RLT was able to predict the survival outcomes, similarly also volumetric data by PSMA PET/CT demonstrated a prognostic utility, in diverse time points (early, interim and end-of-treatment).
[177Lu]Lu-PSMA SPECT/CT alone or in combination with PSA can be helpful in monitoring the response to PSMA-RLT, similarly also PSMA PET/CT; however, a highly heterogeneity across the studies required prospective trials.
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2026 May 14 [Epub ahead of print]
Priscilla Guglielmo, Atena Aghaee, Sajjad Sadeghpour, Amy Eccles, Laura Evangelista
Nuclear Medicine Unit, Humanitas Gavazzeni, Bergamo, Italy - ., Nuclear Medicine Department, Nuclear Medicine Research Center, Mashhad University of Medical Science, Mashhad, Iran., Department of Radiology, Charing Cross Hospital, Imperial College Health Care NHS Trust, London, UK., Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.