Radiosynthesis and preliminary biodistribution in mice of 6‐deoxy‐6‐[¹³¹I]iodo‐L‐ascorbic acid

Abstract

An ascorbate analog labeled with iodine-131, 6-deoxy-6-[131 I]iodo-L-ascorbic acid was prepared for evaluation as an in vivo tracer of L-ascorbic acid. The no-carrier-added radiosynthesis was conducted by nucleophilic bromine-iodine exchange between the brominated precursor and sodium [131 I]iodide in 2-pentanone at 130-1401C. HPLC purification using a reversephase column gave 6-deoxy-6-[ 131 I]iodo-L-ascorbic acid in radiochemical yield of 36-60% with high radiochemical purity and satisfactory-specific radioactivity in a total preparation time of 90 min. Biodistribution studies in fibrosarcoma-bearing mice showed a high uptake in the adrenal glands, accompanied by low activity of tumor accumulation, accumulation properties similar to previous results obtained with 14 C-labeled ascorbic acid and 6-deoxy-6-[ 18 F]fluoro-L-ascorbic acid, in spite of high level of deiodination.

5-O-(4-[125I]Iodobenzyl)-L-ascorbic Acid: Electrophilic Radioiodination and Biodistribution in Mice

“…Recent studies have shown that high-grade tumor tissue has reduced capacity to accumulate AsA relative to normal tissue. 23) On the other hand, contrary to our expectations, the maximum adrenal uptake of radioactivity (12.52±2.52 ID%/g) was seen at 2 min postinjection, which was 3.9-fold lower than that observed for IAsA in mice at the same time point, 14) and then it rapidly decreased to 2.20±1.44 ID%/g at 30 min after injection with an adrenalto-liver ratio of only 0. 4 IAsA, all of which showed the preferential uptake of radioactivity in the adrenal glands.…”

“…There was a somewhat slower clearance of the radioactivity from the blood when compared to 6-18 FAsA 10-13) and 6-131 IAsA 14,15) studied previously. The accumulation of radioactivity in selected organs was highest in the kidneys>liver>lungs>adre nals>heart at 2 min postinjection and then the radioactivity levels gradually decreased with time, similar to those seen for [6][7][8][9][10][11][12][13][14][15][16][17][18] FAsA and 6-131…”

“…Moreover, tumor accumulation in the fibrosarcoma was not significant, also similar to those of [6][7][8][9][10][11][12][13][14][15][16][17][18] FAsA and IAsA. Recent studies have shown that high-grade tumor tissue has reduced capacity to accumulate AsA relative to normal tissue.…”

“…In previous studies, we reported the synthesis of several AsA analogs, focusing on the introduction of radioisotopes such as 18 F and 131 I at the C-6 position of the AsA core, and their potential imaging characteristics were also evaluated in rodents. Among them, 6-deoxy-6-[ 18 F]fluoro-L-ascorbic acid (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) FAsA) [10][11][12][13] and 6-deoxy-6-[ 131 I]iodo-L-ascorbic acid IAsA) 14,15) showed the expected distribution of highest uptake in the adrenal glands in rodents, a neuroendocrine organ that is known to highly express the SVCT-2 transporter, 16) thus demonstrating their suitability as radiotracer analogs of AsA. However, the application of these radiotracers as brain-targeted imaging probes for in vivo studies was found to be limited because of their poor delivery from blood circulation into the brain.…”

6-Deoxy-6-[¹³¹I]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

“…34) To further obtain information on the in vivo behavior of this radiotracer, this paper deals with biodistribution studies in normal rats by both the dissection procedure and whole-body autoradiography. In addition, we performed dis- Normal female rat distribution studies showed high and specific uptake of 6-deoxy-6-[ 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.…”