S24 Abstracts / Nuclear Medicine and Biology 72–73/S1 (2019) S1–S67 Reference: [1] Wang Y, Zhu J, Song X, Wang X, Yang J, and Zhang J. Synthesis and evaluation of 99m Tc–2-[(3-carboxy-1-oxopropyl)amino]-2- deoxy-d-glucose as a potential tumor imaging agent. Bioorganic & Medicinal Chemistry Letters 2014;24:3882-5. PP#61 Assessment of 99m Tc/ 186 Re-tricarbonyl-NODAGA and NOTA complexes in the design of radiolabeled somatostatin receptor-targeting agents G. Makris a , L. Radford b , M. Kuchuk a , F. Gallazzi c , S. Jurisson b , Ch. Smith d , H. Hennkens a a Research Reactor Center, University of Missouri, Columbia, Missouri, United States b Department of Chemistry, University of Missouri, Columbia, Missouri, United States c Molecular Interaction Core, University of Missouri, Columbia, Missouri, United States d Research Service, Harry S. Truman Memorial Veterans’ Hospital; Department of Radiology, University of Missouri School of Medicine; Columbia, Missouri, United States Corresponding Author: hennkensh@missouri.edu To develop hydrophilic peptide complexes labeled via bifunctional chelators (BFCs) with the fac-[M(CO) 3 ] + core (M= Re, 99m Tc, 186 Re), we investigated the utilization of the well-known NODAGA and NOTA macrocylic systems. We report herein fac-[M(CO) 3 (L)] + complexes, both small molecule models for full structural characterization [pyrrolidine-conjugated analogues; L = NODAGAPyr (1), NOTAPyr (2)] and bioconjugates employing a potent somatostatin receptor subtype 2 (SSTR2) targeting peptide antagonist (sst2ANT, 4-NO 2 -Phe- c(DCysTyrDTrpLysThrCys)DTyr-NH 2 [1]) for evaluation of theranostic potential in SSTR2-expressing cancers [L = NODAGAsst2ANT (3), NOTAsst2ANT (4)]. Re(1-4) complexes were synthesized and characterized spectroscopically. [ 99m Tc]Tc(1-4) complexes were prepared in high radiochemical yields (>80%) and were identified by HPLC co-elution with the Re(1-4) references. All 99m Tc complexes were found intact in vitro in rat serum and against 1mM histidine or cysteine through 24h under physiological conditions. [ 186 Re] Re(1-4) complexes, which were prepared and characterized in similar fashion as their 99m Tc surrogates, displayed identical in vitro behavior. Biodistributions were performed in mice bearing AR42J xenografts, and tumor uptake at 1h (% ID/g) was 3% for [ 99m Tc]Tc3 and an impressive 17% for [ 99m Tc]Tc4, with moderate retention for both complexes. Blocking studies indicated receptor-mediated tumor uptake. Non-specific uptake in tissues/organs was low and rapid clearance was observed, predominantly via the renal system. Moreover, SPECT/CT imaging supported the biodistribution data. Our findings establish NODAGA and NOTA as excellent BFCs for the fac- [M(CO) 3 ] + core, and [ 99m Tc]Tc4 shows potential in the development of theranostic agents for SSTR2-expressing tumors. PP#62 Rhenium(I) DNA-intercalating complexes as anticancer agents M. Kaplanis a , I. Roupa a , B. Mavroidi a , M. Paravatou-Petsotas a , M. Pelecanou a , I. Pirmettis a , M. Papadopoulos a a National Centre for Scientific “Demokritos”, Athens, Greece Corresponding Author: mikekaplanis@hotmail.com Despite the growing body of research, cancer remains among the leading causes of death in the world. Cancer treatment depends on the type, stage and location of tumor, but most patients undergo chemotherapy either as the main treatment or in combination with surgery and/or radiotherapy. In this field, metal-based drugs have proven to be extremely promising anticancer agents. Recently, rhenium complexes have been reported as potential agents for the development of anticancer drugs [1].In this work, a new series of complexes of the type fac-[Re(CO) 3 (NN)(X)] 0/+ , where the NN bidentate ligand is 7-fluorodipyrido[3,2-a:2’,3’-c]phenazine (F-dppz, 1) or benzo[i]dipyrido[3,2-a:2’,3’-c]phenazine (dppn, 2) which are known intercalators, is reported. The monodentate (X) ligand is Br (complexes 1a and 2a) or 1,3,5-triaza-7-phosphaadamantane (PTA) (complexes 1b and 2b) or cyclohexyl isocyanide (cisc) (complexes 1c and 2c). All complexes were characterized by NMR, IR spectroscopies and elemental analysis. The DNA-binding studies revealed that all complexes strongly interact with CT-DNA through intercalation. The cytotoxicity studies against cancer cells show moderate toxicity for the PTA-complexes 1b and 2b, but strong toxicity for the cisc- complexes 1c and 2c (IC 50 in order of 1 μM in Hela and MCF7 cancer cell lines) revealing the crucial role of the monodentate ligand X. The analogous to 1a 99m Tc complex 1a* was synthesized in high yield and characterized by comparative HPLC studies using 1a as reference. Further biological evaluation experiments are in progress. Acknowledgments: This Publication is supported by the program of Industrial Scholarships of Stavros Niarchos Foundation. Reference: [1] Leonidova A, Gasser G. Underestimated Potential of Organometallic Rhenium Complexes as Anticancer Agents. ACS Chem. Biol. 2014; 9:2180-2193. PP#63 Synthesis of [ 99 TcX(CO) 5 ] (X = Cl, Br, I) at ambient pressure A. Miroslavov a , H. Braband b , G. Sidorenko a , E. Stepanova a , A. Lumpov a , R. Alberto b a JSC Khlopin Radium Institute, St. Petersburg, Russia b University of Zurich, Zurich, Switzerland Corresponding Author: amiroslav@mail.ru Technetium carbonyls are of much interest for fundamental chemistry and for nuclear medicine. In the commonly used procedures for preparing metal carbonyl complexes, the key step is high-pressure carbonylation of appropriate inorganic precursor. A low-pressure synthesis of Tc carbonyl complexes would be convenient for groups without laboratories specialized for high- pressure syntheses of radioactive material. In this study, we present an atmospheric-pressure procedure for preparing [ 99 TcX(CO) 5 ]. The procedure is described with an example of bromide derivatives. First K 2 [ 99 TcBr 6 ] was prepared by reduction of NH 4 TcO 4 with HBr in the presence of KBr. Then K 2 [ 99 TcBr 6 ] was heated in a 2:1 HCOOH-H 2 SO 4 mixture at 170–180°C for 1 h. After cooling under residual CO the reaction mixture was extracted with DCM. The 99 Tc NMR spectrum of this extract displayed a strong and sharp 99 Tc NMR signal at –1802 ppm (vs. [ 99 TcO 4 ] - ) and a weak broad signal at –1030 ppm. The former signal is assigned to [ 99 TcBr(CO) 5 ], the latter to [TcBr(CO) 4 ] 2 . The solution IR spectrum of the extract displayed the three bands typical for [ 99 TcBr(CO) 5 ] at 2152.4 (vw), 2057.9 (s) and at 2000 (m) cm –1 . Very weak bands of the dimer were observed at 2117.7 cm –1 . The yield of [ 99 TcBr(CO) 5 ] was 27%. [ 99 TcCl(CO) 5 ] was prepared analogously in yield of 15-20% but starting with K 2 99 TcCl 6 . Treatment of K 2 99 TcI 6 along the above procedure yielded a reddish solid which is a mixture of 99 TcI(CO) 5 and [ 99 TcI(CO) 4 ] 2 . In this case the product is contaminated with I 2 .