[Tc]Cyclo(L-homocysteinyl-N-methyl-L-phenylalanyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl), (1‡1´)-sulfide with 3-[(mercaptoacetyl)amino]-L-alanyl-L-lysyl-L-cysteinyl-L-lysinamide

Somatostatin receptors (SSTRs) are implicated in the development of various cancerous tumors of endocrine origin, including those found in the lungs (1, 2). Five types of SSTRs, designated as SSTR1 to SSTR5, have been identified, and the frequency and expression pattern of each receptor type were reported to change with the tumor type (3, 4). On the basis of histological criteria, endocrine carcinomas may show low or intermediate differentiation or could be of the nondifferentiated type; individuals with the latter type of tumor usually have a poor prognosis (1, 5). Activation of the SSTR by the binding of somatostatin (SS) usually inhibits the production of hormones from various glands, and investigators have attempted to use SS for the treatment of various diseases, including endocrine cancers. However, SS has a short plasma half-life because of rapid enzymatic degradation, which makes SS ineffective for such therapy (6). Therefore, the development of SS analogs that are resistant to enzymatic degradation but have a biological activity similar to SS has led to the evaluation of such analogs for the diagnosis and treatment of cancerous tumors of endocrine origin (7-9). Octreotide, a synthetic analog of SS, was approved by the United States Food and Drug Administration (FDA) for the treatment of hormone hypersecretion in individuals suffering from acromegaly and gastropancreatic and carcinoid tumors (10). This molecule was subsequently radiolabeled with isotopes of indium (In) and iodine (I) and has been shown to be a useful agent for the detection of small primary neuroendocrine tumors or their metastasized forms, which are visualized by conventional means (11, 12). However, although these radionuclides are available yet they are expensive to produce. Because radioactive technetium (Tc) is cheaper to produce and yields better images compared with In- or I-labeled compounds, Vallabhajosula et al. decided to use Tc to label SS analogs for preclinical evaluation in rats bearing SS-positive tumors (13). One such SS analog, depreotide, also known as peptide P829, is a tetrapeptide attached to a cyclic hexapeptide that was labeled with Tc to produce [Tc]Depreotide. [Tc]Depreotide has been shown to have a high affinity for SSTR2, SSTR3, and SSTR5 (14). The peptide is commercially available as a kit in Europe and is approved for scintigraphic imaging of malignant lung tumors in conjunction with computed tomography (CT) (9). In the United States this radiochemical is approved by the FDA for the evaluation of indeterminate nodules in the lungs (15).