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-[125 I] iodobenzyl)-L-ascorbic acid ([ 125 I]1) was prepared through a two-step sequence which involved radioiododestannylation 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 [ 125 I]1 in tumor-bearing mice showed signs of distribution profiles similar to the reported results for 6-deoxy-6-[18 F]fluoro-L-ascorbic (6-18 FAsA) acid and 6-deoxy-6-[131 I]iodo-L-ascorbic acid (6-131 IAsA) 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 [ 125 I]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.

A fluorophore-conjugated ascorbic acid functions for the visualization of sodium vitamin C transporters in living cells

“…[12][13][14][15] Therefore, intracellular SVCT monitoring and detection can provide valuable information for biological diagnosis, adaptive therapy and drug discovery. [16][17][18] In this regard, live-cell imaging of SVCTs is meaningful because it can provide high spatiotemporal resolution for the analysis of SVCT dynamics, and reect the ascorbate transporters expression levels, subcellular distribution and spatiotemporal dynamics. Up to now, the options for live cell labelling of SVCTs were very limited.…”

Radiotracers for Nuclear Imaging of Reactive Oxygen Species: Advances Made So Far

“…49 Additionally, 5-O-(4-[ 125 I]iodobenzyl)-L-ascorbic acid (probe [ 125 I]18, Figure 9) was synthesized with a tributylstannyl precursor at 61% overall RCY. 50 The biodistribution results revealed low tumor uptake of In addition, 6-deoxy-6-131 I-iodo-L-ascorbic acid (probe [ 131 I] 14, Figure 9) was prepared by exchanging radioiodine with bromide at RCY of 36−60%. 51,52 The biodistribution of [ 131 I] 14 in fibrosarcoma-bearing mice was similar to that in [ 14 C]11 and [ 18 F]12, and the uptake in the tumor was much lower than that in adrenal glands.…”

“…Furthermore, Yamamoto et al also synthesized several radioiodinated ascorbic acids, including 125/131 I-labeled 2- O -, 3- O - m -iodobenzyl (probe [ 125/131 I] 15 , [ 125/131 I] 16 ), and 6- o - m -iodophenyl (probe [ 125/131 I] 17 ) via isotope exchange at RCYs ranging 12–60% (Figure ). Additionally, 5- O -(4-[ 125 I]­iodobenzyl)- l -ascorbic acid (probe [ 125 I] 18 , Figure ) was synthesized with a tributylstannyl precursor at 61% overall RCY . The biodistribution results revealed low tumor uptake of [ 125/131 I] 15 , [ 125/131 I] 16 , and [ 125 I] 17 , in contrast to higher tumor uptake of [ 125/131 I] 12 .…”