Cu-4,11-Bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-p-Cl-Phe-cyclo(D-Cys-Tyr-D-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH

Somatostatin (SST) is an inhibitor of the release of somatotropin, glucagon, insulin, gastrointestinal hormones, and other secretory proteins (1). SST is also known as somatotropin release-inhibiting factor (SRIF). SSTR is a cyclic polypeptide with two biologically active isoforms, SRIF-14 and SRIF-28, of 14 and 28 amino acids, respectively. SRIF has a short plasma half-life of <3 min (2). SSTR receptors (SSTRs) (G-protein–coupled) have been found on a variety of neuroendocrine tumors and cells of the immune system, and five individual subtypes (SSTR1–SSTR5) have been identified and subsequently cloned from animal and human tissues (3, 4). SSTR also inhibits cell proliferation and promotes apoptosis through binding to specific cell-surface SSTRs (5). In-Diethylenetriamine pentaacetic acid-octreotide (In-DTPA-OCT) is an SST analog that, over the last decade, has remained the most widely used radiopharmaceutical and the only FDA approved radiotracer for the scintigraphic detection and staging of primary and metastatic neuroendocrine tumors bearing SSTRs with single-photon emission computed tomography (SPECT) (6). It has also shown promising results in peptide-receptor radionuclide therapy (7). Octreotide (OCT) is a cyclic peptide with eight amino acids. In-DTPA-OCT binds with high affinity to SSTR2 and SSTR5 and to SSTR3 to a lesser degree, but it does not bind to SSTR1 and SSTR4 (8). A large number of radiolabeled SST analogs have been reported using different radionuclides and different linkers. Currently used targeting SSTR peptides mainly are SSTR2 agonists. Therefore, there is a need for SSTR2 antagonist radioligands (9). p-Cl-Phe-cyclo(D-Cys-Tyr-D-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH (LM3) is a novel selective SSTR2 antagonist. Fani et al. (10) prepared Cu-4,11-Bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-LM3 (Cu-CB-TE2A-LM3) as a positron emission tomography (PET) imaging agent for SSTR2.