TY - JOUR T1 - VPAC1 biomarker for imaging triple negative breast cancer JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1282 LP - 1282 VL - 59 IS - supplement 1 AU - Sushil Tripathi AU - Pardeep Kumar AU - YuanYuan Jin AU - Eric Wickstrom AU - Mathew Thakur Y1 - 2018/05/01 UR - http://jnm.snmjournals.org/content/59/supplement_1/1282.abstract N2 - 1282Objectives: Our previous studies in which we used Copper-64 labeled VPAC1 receptor specific PACAP analogue (TP-3805) to image breast cancer (BC) in humans, showed that BC can be imaged at 15 minute post injection with 100% sensitivity and specificity. No triple negative BC (TNBC) were included. The objective here was to determine if 64Cu-TP3805 could be used to image TNBC in nude female mice bearing MDA-MB-231xenografts. Methods: 30 µL of 64CuCl2 in 0.1M HCl, was added to peptide-conjugate (20 µg) in 200 µL of 0.2M glycine buffer (pH=9.27), and incubated at 70°C for 90 min. The radiochemical purity was determined by radio-HPLC. Expression of VPAC1 receptors on MDA-MB-231, along with three other human BC cells lines namely MD-MBA-231, MD-MBA-157, MD-MBA-436 and MD-MBA-468, was determined by western blots. Cell binding assay was performed by incubating 64Cu-TP3805 with 1.5 x 106 MDA-MB-231, human TNBC cells. 107 MDA-MB-231 cells grown in the tissue culture were administered subsequently in the right thigh of the mice (N=5) and tumors were allowed to grow to no more than 6mm in diameter. PET/CT imaging, receptor blocking, and tissue distribution were performed. Results: radio-HPLC showed retention time for 64Cu-peptide at 5.3 min as compared to free 64CuCl2 at 3.4. The radiochemical purity of 64Cu-TP3805 was 96.3 ± 0.5 %. We found strong signal for VPAC1 receptor on western blot (Fig-1). The cell binding for 64Cu-peptide was 83.96 ± 3.5 %. Micro-PET/CT images were analyzed and tissue distribution showed tumor to muscle (T/M) ratio of 5 ± 0.5 post 2h injection. Receptor blocked imaging studies with 64Cu-TP3805 showed ~60% decrease in T/M (1.9 ± 0.2). The tissue distribution showed a similar pattern as observed in PET imaging. Conclusions: Western blot studies confirmed high VPAC1 expression on the TNBC cells lines examined. TP3805 showed excellent labeling efficiency, and high uptake in TNBC cells. Receptor blocking confirmed the specificity of the 64Cu-TP3805 for the VPAC1 receptors in TNBC cells, which makes it a highly suitable biomarker to image TNBC. Acknowledgments: The research, in part, was supported by NIH/NCI RO1CA157372 (MLT), NIH/NCI 1S10OD012406 (MLT) and NIH/NCI S10RR23709 (MLT). References 1- VPAC1 Receptors for Imaging Breast Cancer: A Feasibility Study. J Nucl Med. 2013 Jul;54(7):1019-25, Mathew L. Thakur, Kaijun Zhang, Adam Berger, Barbara Cavanaugh, Sung Kim, Chaitra Channappa, Andrea J. Frangos, Eric Wickstrom and Charles M. Intenzo. ER -