First systematic mapping of non-target [68Ga]Ga-DOTANOC uptake across anatomical sites and etiologies

Abstract Objectives This systematic review describes the spectrum, distribution, and etiologies of non‑target [68Ga]Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-1-Nal³-octreotide ([68Ga]Ga‑DOTANOC)‑avid lesions proven by histopathology or follow‑up to be unrelated to normal biodistribution or the primary somatostatin receptor‑expressing disease. Methods PubMed, Web of Science, and Scopus databases were utilized to conduct a systematic search and were updated until May 31, 2025. Three authors independently screened the titles and abstracts of the retrieved articles and selected the articles on the basis of the inclusion and exclusion criteria. Results Seventy-six eligible studies encompassing 542 patients reported 799 non-target [68Ga]Ga-DOTANOC-avid findings. Nononcologic causes accounted for the majority (59.6%), with malignant oncologic and benign tumorous etiologies accounting for 30.2% and 10.3%, respectively. The abdomen was the most common anatomical site (38%), followed by the thorax (21.6%), head/neck (18.1%), and musculoskeletal system (13.1%), whereas pelvic involvement was least common (9%). Conclusions Abdominal non-target [68Ga]Ga-DOTANOC-avid findings represent a major interpretive challenge in [68Ga]Ga-DOTANOC PET/CT, as these findings often overlap with NET-predominant regions. Recognition of these patterns can increase diagnostic accuracy and support broader clinical integration of [68Ga]Ga-DOTANOC beyond its conventional utility. Advances in knowledge This systematic review clarifies anatomy-based and etiology-based non-target findings that can be encountered in [68Ga]Ga-DOTANOC PET imaging. Non-target findings with [68Ga]Ga-DOTANOC, while challenging, may expand its use beyond NETs and meningiomas, opening new diagnostic avenues.