Novel PET tracers to distinguish the nature of residual masses after the completion of chemotherapy in metastatic testicular germ cell tumours: A systematic review

Abstract Background Testicular germ cell tumours (TGCTs) are the most common malignancy in young adult males. After chemotherapy, the evaluation of residual masses is critical. However, the current standard imaging modality, [ 18 F]-FDG PET, has limited specificity—particularly in distinguishing viable tumour from necrosis or mature teratoma. This limitation often leads to unnecessary surgery or misinterpretation of treatment response. Objectives This systematic review aims to explore and evaluate novel PET tracers that could improve diagnostic accuracy in TGCTs, especially in post-chemotherapy settings. Methods A comprehensive literature search was conducted on PubMed and Scopus through December 2025, using terms including “testicular,” “germ cell tumour,” “PET scan,” and “novel.” Studies focusing solely on [ 18 F]-FDG were excluded. Preclinical studies, case reports, and clinical trials investigating alternative PET tracers or relevant molecular targets (e.g., ghrelin, claudin-6) were included. The quality of selected articles was assessed by using CASP for the qualitative research. Results A total of 17 studies met the inclusion criteria. Emerging PET tracers evaluated include [ 18 F]-FLT, FAPI, αvβ3-integrin-targeted agents, [ 18 F]-fluciclovine, PSMA-targeted tracers, and those based on ghrelin and claudin-6. Among these, αvβ3-targeted imaging has shown promising preclinical results in differentiating mature teratoma from necrosis. Ghrelin receptor tracers appear promising due to their high expression in TGCTs, although they remain in preclinical development. Claudin-6, a tight-junction protein, is highly expressed in most TGCT histologies and may be a viable molecular target, as supported by early-phase clinical trials. Conclusions Novel PET tracers represent a promising avenue to refine TGCT management. αvβ3-integrin and ghrelin-based tracers are particularly noteworthy for their potential to guide decision-making after chemotherapy. However, further clinical validation is required before routine implementation. These innovations could significantly reduce overtreatment and enhance personalized care in TGCT patients.