Radiolabeled Somatostatin Analogs for Cancer Imaging

Somatostatin receptors (SSTR) are expressed by many tumours especially those related to neuro-endocrine origin and molecular functional imaging of SSTR expression using radiolabelled somatostatin analogs have revolutionized imaging of patients with these group of malignancies. Coming a long way from the first radiolabelled somatostatin analog ¹²³I-Tyr-3-octreotide, there has been significant developments in terms of radionuclides used, the ligands and somatostatin derivatives. ¹¹¹In-Pentetreotide extensively employed for imaging NETs at the beginning has now been replaced by ⁶⁸Ga-SSA based PET-CT. SSA-PET/CT performs superior to conventional imaging modalities and has evolved in the mainframe for NET imaging. The advantages were multiple: (i) superior spatial resolution of PET versus SPECT, (ii) quantitative capabilities of PET aiding in disease activity and treatment response monitoring with better precision, (iii) shorter scan time and (iv) less patient exposure to radiation. The modality is indicated for staging, detecting the primary in CUP-NETs, restaging, treatment planning (along with FDG: the concept of dual-tracer PET-CT) as well as treatment response evaluation and follow-up of NETs. SSA PET/CT has also been incorporated in the guidelines for imaging of Pheochromocytoma-Paraganglioma, Medullary carcinoma thyroid, Meningioma and Tumor induced osteomalacia. At present, there is rising interest on (a) ¹⁸F-labelled SSA, (b) ⁶⁴Cu-labelled SSA, and (c) somatostatin antagonists. ¹⁸F offers excellent imaging properties, ⁶⁴Cu makes delayed imaging feasible which has implications in dosimetry and SSTR antagonists bind with the SST receptors with high affinity and specificity, providing high contrast images with less background, which can be translated to theranostics effectively. SSTR have been demonstrated in non-neuroendocrine tumours as well in the peer-reviewed literature, with studies demonstrating the potential of SSA PET/CT in Neuroblastoma, Nasopharyngeal carcinoma, carcinoma prostate (neuroendocrine differentiation) and lymphoma. This review will focus on the currently available SSAs and their history, different SPECT/PET agents, SSTR antagonists, comparison between the various imaging tracers, and their utility in both neuroendocrine and non-neuroendocrine tumors.