Background: 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.
Methods: 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.
Results: 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).
Conclusions: [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.