Ga-68 Labeled Somatostatin Analogs Positron Emission Tomography/ Computed Tomography in Gastroenteropancreatic Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are characterized by the heterogeneous nature, frequently indolent course and possibility of multiple and variable anatomic sites of the primary tumor. Somatostatin is a cyclic peptide consisted of 14 amino acids and produced by neuroendocrine, immune, and inflammatory cells. The cerebral cortex, the brain stem, the hypothalamus, the pancreas and the gastrointestinal tract are physiological production sites. SSTRs are a family of G-proteincoupled receptors that comprises five subtypes (SSTR1-5) [1,2]. Well/moderately differentiated NETs are generally overexpress somatostatin receptors (SSTRs) [3]. Because of the overexpression of SSTRs the radiolabeled somatostatin analogs can be used to localize the primary tumor and its metastasis. The imaging of the SST subtype 2 (SST2) has been developed and has had clinical applications [4]. The majority of NETSs expresses SSTR types 1, 2, 3, and 5 [5]. SSTR2 is the dominant expressed subtype in pancreatic endocrine or carcinoid tumors [6]. Somatostatin receptor imaging is widely used for the diagnosis, staging and restaging of NETs [7]. Firstly, somatostatin receptor scintigraphy with Tc-99m and In-111 labeled somatostatin analogs have been used for the evaluation of NETs [8,9]. After development of Ga-68 labeled somatostatin analogs, in most centers in Europe positron emission tomography (PET) with Ga68 labeled somatostatin analogs have been utilized due to higher resolution of PET imaging. Ga-68 is a positron emitter radio metal with convenient labeling characteristics and it can be easily obtained from Ge-68/Ga-68 generator system [10]. Because of different somatostatin receptor subtype expression of different neuroendocrine tumors, different synthetic somatostatin analogs with different SSTRs subtype affinities have been developed such as DOTA-D-Phe1-Tyr3-octreotide (DOTATOC), DOTA1-Nal3octreotide (DOTANOC) and DOTA-D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) (Figure 1). Previous studies have established the efficacy of this Ga-68 labeled DOTA-peptides in the diagnosis of NETs [11-15].