Research & Industry Reports

Targeting VPAC1 Receptors for PET Imaging of Breast Cancer

By Mathew Thakur, PhD, Thomas Jefferson University Hospital, Philadelphia, PA

Annually in the USA approximately 7 million breast biopsies are performed, approximately 80% of which (5.6 million) find benign pathology. Th e need is compelling to investigate improved imaging probes that might target specific biomarkers and thereby contribute to a greater reliability and higher sensitivity and specificity for imaging.

VPAC1 receptors are overexpressed on malignant cells before cell morphology is altered and in higher density than on the normal breast tissue cells. These receptors are internalised, phosphorylated and are not reexpressed on the cell membrane. These data render VPAC1 receptors as highly useful biomarkers that may be targeted for noninvasive PET imaging. The confirmation of the presence of these fingerprints on a suspected mass will ascertain malignancy and the absence of a benign pathology.

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide have high affinity for VPAC1, VPAC2 and PAC1 receptors overexpressed on human cancer cells. Four potent analogues of these peptides, TP3939, TP3982, TP4200 and TP3805 were labeled with 64Cu and evaluated exvivo and invivo to assess their biological activity and receptor specificity. The ultimate goal is to utilize 64Cu analogues for positron emission tomography (PET) imaging of breast cancers in humans.