Agonist Trap Unmasked

A 22-year-old woman with a neuroendocrine tumor underwent 68Ga-DOTANOC PET/CT, revealing incidental uterine fibroid uptake mimicking pelvic metastasis. The fibroid's hyperavidity posed diagnostic ambiguity, indistinguishable from low-grade NET deposits. Crucially, subsequent 68Ga-NODAGA-JR11 (SSTR antagonist) PET/CT demonstrated preserved tumor detection but absent fibroid uptake, unequivocally confirming benign leiomyoma. This striking discordance unveils agonists' internalization trap-prolonged DOTANOC retention through SSTR2 endocytosis in estrogen-primed fibroids-versus antagonists' precision: surface binding without non-specific accumulation. In fibroids, the lack of antagonist binding-despite agonist positivity-arises from inadequate receptor density to support sustained surface binding, thereby eliminating false-positive results. Dual SSTR imaging redefines diagnostic certainty, averting interventions while optimizing theranostics.