PT - JOURNAL ARTICLE AU - Pardeep Kumar AU - Sushil Tripathi AU - Mathew Thakur TI - A comparison of in vivo stability of Ga-68 labeled peptide conjugate for targeting VPAC receptors. DP - 2018 May 01 TA - Journal of Nuclear Medicine PG - 1298--1298 VI - 59 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/59/supplement_1/1298.short 4100 - http://jnm.snmjournals.org/content/59/supplement_1/1298.full SO - J Nucl Med2018 May 01; 59 AB - 1298Objectives: In our previous studies, we labeled gallium-68 (Ga-68) with NODAGA and DOTA-peptide conjugates and noted their relatively low in vivo stability. Objective was to enhance the stability, we have labeled with Ga-68 a diaminedithiol (N2S2)-peptide conjugate, (TP-3805), and examined its in vivo stability, receptor binding, PET/CT imaging and tissue distribution in athymic nude mice bearing human breast cancer (BC) xenografts. Methods: TP-3805 was custom prepared by Bachem (USA) and characterized by electrospray mass spectrometry. TP-3805 was radiolabeled with Ga-68 and radiochemical purity was evaluated by radio-HPLC. The transmetallation study was performed by incubating Ga-68-TP-3805 with 100 nM Fe3+/Zn2+/Ca2+ ionic solution. For in vivo stability, 100 ± 20 μCi of Ga-68-TP-3805 was injected intravenously into the athymic nude mice (n =3) and mice were sacrificed one hr. later. Plasma was separated, plasma proteins was precipitated with ethanol/chloroform (4:1) mixture, and supernatant was analyzed by HPLC. Receptor specificity was determined ex vivo by cell binding assay using human BT474 BC cells. PET/CT imaging and tissue distribution studies were carried out in mice bearing BT474 xenografts (n = 5). Results: As determined by MALDI-TOF, the purity of the peptide conjugate was 99.9% with M.W. 3805 Da. Radio-HPLC showed retention time for Ga-68-TP-3805 at 5.6 ± 0.3 min as compare to Ga-68-Cl3 at 3.4 ± 0.4 min. The radiolabeling efficiency for Ga-68-TP-3805 was 96.3 ± 0.7 %. The chelate was stable against any transmetallation (95.5 ± 1.8 %). The in vivo stability was 96.2 ± 0.8 % at 60 min which is significantly better (p < 0.001) than Ga-68 labeled NODAGA-peptide (2.1 ± 0.2 %) and DOTA-peptide (1.4 ± 0.3%). PET/CT images at 1hr post injection showed insignificant difference (p = 0.2) between tumor to muscle (T/M) ratio 3.1 ± 0.4 for Ga -68-TP-3805 and 3.4 ± 0.3 for Ga-68-NODAGA-peptide. The T/M ratio however, was significantly greater (p = <0.05) for Ga-68-TP-3805 than for the DOTA-peptide (1.8 ± 0.7) For Ga-68-TP3805 the %ID/G for liver was 12.2 ± 0.8, lungs 10.2 ± 0.5, intestine 4.5 ± 0.4 and kidney 1.3± 0.3. The kidney uptake for Ga-68-TP3805 was significantly favorable (P=<01) than that for NODAGA (70± 9.2) and for DOTA (40.3± 5.8) peptide. Conclusion: The greater in vivo stability and the lower kidney uptake of the Ga-68-TP-3805 were the key findings of the study. For us therefore Ga-68-TP-3805 is the preferred agent for PET imaging of BC. Support: The research, in part, was supported by NIH/NCI RO1CA157372 (MLT), NIH/NCI 1S10OD012406 (MLT) and NIH/NCI S10RR23709 (MLT).