111In-Tetrameric Plectin-1 targeting peptide (4(βAKTLLPTP-GGS(PEG5000))KKK-111In-DOTA-βA-NH2)

Patients with pancreatic ductal adenocarcinoma (PDAC) have a median survival of 6 months and a 5-year survival rate of only 3% (1). PDAC is an aggressive cancer with early metastasis in >80% of patients. Early detection would be particularly useful for monitoring people at high risk of developing pancreatic cancer. Plectin-1 was identified in 100% of tested PDAC lesions and 60% of tested preinvasive PanIN III lesions (2). Plectin-1, a cytoskeletal component, is not expressed in the normal pancreas, liver, lymph node, lung, or peritoneum in humans. Using phage display screenings, the linear peptide Lys-Thr-Leu-Leu-Pro-Thr-Pro (KTLLPTP) (Plectin-1–targeting peptide, PTP) (3) has been found to specifically bind to Plectin-1 (4, 5), a protein present both inside and on the membrane of human and mouse PDAC cells but only on the inside of normal pancreatic cells. Kelly et al. (3) conjugated PTP to Cy5.5-labeled cross-linked iron oxide particles (CLIO-Cy5.5) for imaging Plectin-1 expression in PDAC, which suggests that Plectin-1 can serve as a biomarker for PDAC. Bausch et al. (2) labeled a tetrameric PTP with 111In (4(βAKTLLPTP-GGS(PEG5000))KKK-111In-DOTA-βA-NH2) (111In-tPTP) for single-photon emission computed tomography (SPECT) imaging for primary and metastatic pancreatic tumors.