5-O-(4-[ 125I]iodobenzyl)-L-ascorbic acid: Electrophilic radioiodination and biodistribution in mice

Abstract

As a part of our efforts to develop potential imaging agents for ascorbate bioactivity, 5-O-(4-[ 125I] iodobenzyl)-L-ascorbic acid ([ 125I]1) was prepared through a two-step sequence which involved radioiodo-destannylation of a protected tributylstannyl precursor 6, followed by hydrolysis in acidic methanol of the protecting groups in 61% overall radiochemical yield, with a radiochemical purity of over 98% and a specific activity of more than 15.4 GBq/μmol. Tissue distribution of [ 125I]1 in tumor-bearing mice showed signs of distribution profiles similar to the reported results for 6-deoxy-6-[ 18F]fluoro-L-ascorbic (6- 18FAsA) acid and 6-deoxy-6-[ 131I]iodo-L-ascorbic acid (6- 131IAsA) but with notable differences in the adrenal glands, in which considerably lower uptake of radioactivity and rapid clearance with time were observed. Pretreatment of mice with a known inhibitor of ascorbate transport, sulfinpyrazone, did not produce any significant change in the adrenal uptake of radioactivity after injection of [ 125I]1 compared to the control, suggesting that uptake in the adrenal glands is independent of the sodium-dependent vitamin C transporter 2 transport mechanism. Introduction of a bulky substituent at C-5 on AsA, such as an iodobenzyloxy group, may not be suitable for the design of analogs that may still be able to maintain characteristic distribution properties in vivo seen with AsA itself. © 2012 The Pharmaceutical Society of Japan.