Synthesis of radiolabeled cytarabine conjugates

N4-Modified, novel Ara-C conjugate capable of radiolabeling with gamma ray-emitting (99mTc) as well as positron emitting (18F) radionuclides, that is, N4-hydrazine derivative was synthesized. The radiolabeling of N4-(hydrazinonicotinyl)-1-β-arabinofuranosyl cytosine (HAra-C) with 99mTc was performed with over 95% labeling yield. To label HAra-C with 18F, 4-fluoro(18F)-benzaldehyde was synthesized from 4-formyl-N,N,N-trimethylanilinium triflate in 30% radiochemical yield; it quantitatively formed hydrazone derivative with HAra-C within 45 min. The radiolabeled conjugates were analyzed by radio-UV-RP-HPLC. The cold precursors were characterized by 1H, 13C NMR. Additionally, HAra-C was evaluated for cytotoxicity in lung adenocarcinoma (H441) cells and found to be comparable in cell killing efficiency to that of Ara-C. Uptake of 99mTc-HAra-C in cultures of H441 cells and sensitive pancreatic cancer cells (MIAPaCa-2) was inhibited by nucleoside transporter inhibitor nitrobenzylthioinosine. The results suggest that 99mTc-labeled HAra-C is a substrate for the membrane nucleoside transporters, and that it may be used in molecular imaging of nucleoside transporter expression for the verification of potential anticancer efficacy of nucleoside drugs, such as Ara-C and gemcitabine.

N4-Modified Ara-C conjugate, N4-(hydrazinonicotinoyl)-1-β-arabinofuranosyl cytosine (HAra-C) was synthesized and its radiolabeling was performed with 99mTc and 18F in 95% and 30% labeling yields.Figure optionsDownload as PowerPoint slide