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.
Normal female rat distribution studies showed high and specific uptake of 6-deoxy-6-[(131)I]iodo-L-ascorbic acid (6-(131)IAsA) 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-(131)IAsA 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-(131)IAsA, compared to the control, with increased adrenal-to-liver and adrenal-to-kidney ratios. To further characterize 6-(131)IAsA 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-(131)IAsA 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.
Kim
Jintaek
J
Graduate School of Pharmaceutical Sciences, 3-1-1 Maidashi,Higashi-ku, Fukuoka 812-8582, Japan.
Yamamoto
Fumihiko
F
Gondo
Shigeki
S
Yanase
Toshihiko
T
Mukai
Takahiro
T
Maeda
Minoru
M
D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000493:pharmacokinetics; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
C120802:6-deoxy-6-iodoascorbic acid; D007457:Iodine Radioisotopes; D008055:Lipids; D001205:Ascorbic Acid