6-deoxy-6-〔131I〕iodo-L-ascorbic acid for the in vivo study of ascorbate: autoradiography, biodistribution in normal and hypolipidemic rats, and in tumor-bearing nude mice

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  • 6-Deoxy-6-[<sup>131</sup>I]iodo-<small>L</small>-ascorbic Acid for the <i>in Vivo</i> Study of Ascorbate: Autoradiography, Biodistribution in Normal and Hypolipidemic Rats, and in Tumor-Bearing Nude Mice
  • 6 deoxy 6 131I iodo L ascorbic acid for the in vivo study of ascorbate autoradiography biodistribution in normal and hypolipidemic rats and in tumor bearing nude mice

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Normal female rat distribution studies showed high and specific uptake of 6-deoxy-6-[131I]iodo-L-ascorbic acid (6-131IAsA) into the adrenal glands, known to highly express the ascorbate sodium-dependent vitamin C transporter-2 (SVCT-2), and the adrenal gland was clearly visualized by whole-body autoradiography. Preinjection of sulfinpyrazone, a known blocker of ascorbate transport, with 6-131IAsA resulted in decreased uptake of radioactivity in rat adrenal glands compared to the control group, seemingly illustrating the participation of the SVCT transporter (probably the SVCT-2 subtype) in the uptake process in vivo. 4-Aminopyrazolo[3,4-d]pyrimidine-induced hypolipidemic rats showed a 1.7-fold increase in adrenal uptake of radioactivity at 30 min postinjection of 6-131IAsA, compared to the control, with increased adrenal-to-liver and adrenal-to-kidney ratios. To further characterize 6-131IAsA for its tumor uptake properties, biodistribution studies were also performed using male nude mice implanted with either Y-1 adrenocortical tumor cells or adrenal medulla-derived PC12 cells. None of these tumors exhibited relevant uptake of 6-131IAsA while normal adrenal glands showed high uptake of radioactivity, suggesting that these tumors in this model have only a poor transport capacity for this agent. The present study demonstrates that the use of radioiodinated 6-IAsA may help to obtain information about functional alterations in diseased adrenal glands, but it does not exhibit desirable properties as a tumor-seeking agent for ascorbic acid bioactivity.

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