title: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) receptor specific peptide analogues for PET imaging of breast cancer: In vitro/in vivo evaluation.
abstract: 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 (64)Cu and evaluated ex vivo and in vivo to asses their biological activity and receptor specificity. The ultimate goal is to utilize (64)Cu analogues for positron emission tomography (PET) imaging of breast cancers in humans. Radiochemical purity of each analogue was >92%. The muscle relaxivity assay revealed IC(50) to be 5.3x10(-8) M, 4.4x10(-8) M, 8.1x10(-8) M, 8.1x10(-9) M and Kd values determined by receptor specific cell binding assays were 3.3 nM, 0.33 nM, 0.2 nM and 0.72 nM for TP3805, TP3939, TP3982, and TP4200 respectively. The receptor affinity, using human breast cancer tissues, was 10.93 times greater than normal breast tissues. RT-PCR confirmed increased VPAC1 receptor expression on human breast tumor cells over normal cells and corroborated with autoradiography data. The blood clearance was rapid and in vivo translocation of (64)Cu to plasma protein was <15%. Data demonstrate that these analogues are potent, have uncompromised biological activity and are worthy of further evaluation for accurate PET imaging of human breast cancers and in determining malignant and benign lesions.
authors.affiliation: Laboratory of Radiopharmaceuticals and Molecular Imaging, Department of Radiology, Thomas Jefferson University, 1020 Locust Street, Suite 361 JAH, Philadelphia, PA. 19107, USA.
authors.forename: Kaijun
authors.initials: K
authors.lastname: Zhang
authors.forename: Mohan R
authors.initials: MR
authors.lastname: Aruva
authors.forename: Nylla
authors.initials: N
authors.lastname: Shanthly
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Cardi
authors.forename: Chirag A
authors.initials: CA
authors.lastname: Patel
authors.forename: Satish
authors.initials: S
authors.lastname: Rattan
authors.forename: Gregory
authors.initials: G
authors.lastname: Cesarone
authors.forename: Eric
authors.initials: E
authors.lastname: Wickstrom
authors.forename: Mathew L
authors.initials: ML
authors.lastname: Thakur
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D003301:Copper Radioisotopes; D005260:Female; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry*; D049268:Positron-Emission Tomography; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000032:analysis* / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000032:analysis* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives*
chemical_list: D003301:Copper Radioisotopes; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide