title: Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer.
abstract: The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)₃(H₂O)₃]⁺ and (NEt₄)₂[Re(CO)₃Br₃] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. cjy0929@snu.ac.kr.|Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 16229, Korea. cjy0929@snu.ac.kr.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari 70125, Italy. rosamaria.iacobazzi@uniba.it.|Istituto Tumori IRCCS "Giovanni Paolo II", Flacco, St. 65, Bari 70124, Italy. rosamaria.iacobazzi@uniba.it.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Iacobazzi
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari 70125, Italy. mara.perrone@uniba.it.
authors.forename: Mara
authors.initials: M
authors.lastname: Perrone
authors.affiliation: Department of Chemistry, University of Bari "Aldo Moro", Bari 70125, Italy. nicola.margiotta@uniba.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Margiotta
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari 70125, Italy. annalisa.cutrignelli@uniba.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cutrignelli
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. jaehoboa@paran.com.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. ddp2194@naver.com.
authors.forename: Do Dam
authors.initials: do D
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. bsmoon@snu.ac.kr.
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Moon
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari 70125, Italy. nunzio.denora@uniba.it.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Denora
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. kse@snu.ac.kr.|Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 16229, Korea. kse@snu.ac.kr.|Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 16229, Korea. kse@snu.ac.kr.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. leebc@snu.ac.kr.|Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 16229, Korea. leebc@snu.ac.kr.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007697:Kinesics; D061986:MCF-7 Cells; D009369:Neoplasms / Q000000981:diagnostic imaging; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism*; D013667:Technetium / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; D013667:Technetium; C001439:imidazo(1,2-a)pyridine
keywords: 99mTc(CO)3; SPECT; TSPO; TSPO-rich tumors; Tricarbonyltechnetium-99m; translocator protein