PT - JOURNAL ARTICLE AU - Jung Min Kim AU - Byung Chul Lee AU - Nunzio Denora AU - Hyewon Youn AU - Sang Eun Kim TI - Synthesis and evaluation of a new TSPO-binding ligand CB259 for cancer theranostic DP - 2021 May 01 TA - Journal of Nuclear Medicine PG - 1451--1451 VI - 62 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/62/supplement_1/1451.short 4100 - http://jnm.snmjournals.org/content/62/supplement_1/1451.full SO - J Nucl Med2021 May 01; 62 AB - 1451Introduction: Translocator protein 18 kDa (TSPO), which is located on the outer membrane of mitochondria, has been reported to overexpress in various cancer cells, including brain, breast, colon, prostate and ovarian cancers, as well as in astrocytomas and hepatocellular. Therefore, TSPO could be an attractive target for imaging and therapy of TSPO-rich cancer. In this work, we designed and synthesized an imidazo[1,2-a]pyridine analog (CB259) for radiolabeling. The 99mTc-labeled form can be a diagnostic tool and, on the other hand, the 188Re-labeled form can be a therapeutic agent for TSPO-rich cancer diagnosis and treatment, respectively. Methods: The TSPO ligand CB259 was prepared by thiourea ligation of the 4-((N,N-hydroxycarbonyl-2-picolylamino)methyl)aniline moiety to CB86. Compound Re-CB259 was prepared by a coordination of CB259 with (NEt4)2[185/187ReBr3(CO)3] in dimethylformamide at 70 oC for 1 h, followed by HPLC purification. Binding affinity of Re-CB259 for TSPO was measured by displacement of [3H]PK 11195 in the isolated membrane protein from C6 glioma cells. The radiosynthesis of 99mTc-CB259 was conducted in dimethylformamide (350 μL) contains CB259 (0.5 mg, 0.7 μmol) and [99mTc(CO)3(H2O)3]+ at 70 oC for 30 min. 99mTc-CB259 was isolated from the obtained mixture by HPLC purification. Log D of 99mTc-CB259 was determined in the mixture of n-octanol and phosphate buffer (pH 7.4) by shaking vial method. In vitro stability test of 99mTc-CB259 performed in human serum at 37 oC for 4 h. Results: Re-CB259 was prepared with 59.5% yield and its binding affinity (Ki) was 32.1±9.9 nM for TSPO. The radiolabeled form, 99mTc-CB259 was successfully synthesized with 27.6 % radiochemical yield (non-decay corrected) in high radiochemical purity (>99%). The identification of 99mTc-CB259 was confirmed by HPLC co-injection with Re-CB259 as followed the observed HPLC retention time was 17 min for 99mTc-CB259 and 19 min for Re-CB259. 99mTc-CB259 showed high in vitro stability (>99%), and 1.47±0.12 Log D value (n=3). Conclusion: We successfully synthesized and characterized a new TSPO-binding ligand, CB259 for radiolabeling with the matched pair 99mTc/188Re. Further biological evaluations are preparing to validate a potential of CB259 as a cancer theranostic agent.