Decreased Tissue Accumulation of 6-Deoxy-6-[18F]fluoro-L-ascorbic Acid in Glutathione-Deficient Rats Induced by Administration of Diethyl Maleate

CHEMICAL & PHARMACEUTICAL BULLETIN

Kino

Kato

et al. 2012

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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.

Section: Resultssupporting

confidence: 63%

Section: Resultsmentioning

confidence: 65%

mentioning

confidence: 99%

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

CHEMICAL & PHARMACEUTICAL BULLETIN

Kino

Kato

et al. 2012

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Section: )mentioning

confidence: 99%

“…Several AsA analogs labeled with 18 F, 131 I, 125 I, or 99m Tc were prepared and their potential imaging characteristics were evaluated in animals. [25][26][27][28][29][30][31] 6-Deoxy-6-iodo-L-ascorbic acid (6-IAsA) has been shown to be an effective inhibitor of AsA transport, with transport affinity similar to that of AsA, and that it is taken up into cells by a sodium-dependent AsA transporter.32,33) As part of our ascorbate studies, we recently reported the synthesis and preliminary biodistribution in normal mice of 6-deoxy-6-[ 131 I]iodo-L-ascorbic acid (6-131 IAsA), which demonstrates high adrenal uptake in spite of considerable in vivo deiodination. 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.…”

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confidence: 99%

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

Biological & Pharmaceutical Bulletin

Yamamoto

Gondo

et al. 2009

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Over the past few decades, a number of radiopharmaceuticals for noninvasive imaging of the adrenal glands by the nuclear imaging technique have been evolved, designed by targeting specific metabolic or synthetic processes within the gland.1,2) Among the current developments and the expansion of new molecular imaging modalities and specific probes, adrenal scintigraphy using more specific radiotracers to obtain functional information for tissue characterization is still challenging. 3,4)The adrenal gland is among the organs with the highest concentration of L-ascorbic acid (AsA) in the body and is particularly sensitive to deficiencies of AsA.5) It is well known that AsA is an important cofactor required both in catecholamine biosynthesis and in adrenal steroidogenesis, and that it functions as a water-soluble antioxidant in the adrenal gland. [5][6][7][8][9] The cellular uptake of AsA and its distribution in cells are important factors that determine its inherent activity. Studies of tissue distribution of radioactivity in animals after injection of 14 C-labeled AsA ( 14 C-AsA) were reported in the 1960s, showing a remarkable uptake of radioactivity in the adrenal glands, pituitary glands and parotid glands.10-12) Diagnostic application of AsA as a radiotracer for imaging the adrenals, however, remains to be limited by relatively high accumulations of 14 C-AsA in the liver and kidneys. 13)Recent biochemical studies have demonstrated that AsA is taken up into cells by the sodium-dependent vitamin C transporter (SVCT-1 and -2), whereas oxidized vitamin C (dehydroascorbic acid) is transported via glucose transporters. [14][15][16][17][18][19] SVCT-1 is expressed in epithelial organs such as the liver and kidneys, whereas SVCT-2 is found in the adrenal glands and lungs. [14][15][16][17][18][19] In particular, SVCT-2 is primarily responsible for the uptake of AsA from blood circulation into the adrenal cells. [14][15][16][17][18][19] The adrenals have been shown to have the largest falls in the AsA levels in mice with a deficiency of 20) and the influence of the depletion of tissue AsA on tissue catecholamines was found to be most prominent in the adrenals. 21,22) In addition, it has recently been shown that overexpression of adrenal SVCT-2 mRNA in diabetic mice resulted in increased uptake of AsA. 23) Thus, it is most likely that the AsA transport mechanism plays an important role in the pathologic processes of the adrenals. 24) We became interested in the possibility that appropriate structural AsA analogs with specific transport characteristics, if possessing favorable in vivo distribution properties, might be used as tracer agents for the visualization of biochemical events associated with the action of AsA in the adrenal glands. Several AsA analogs labeled with 18 F, 131 I, 125 I, or 99m Tc were prepared and their potential imaging characteristics were evaluated in animals. [25][26][27][28][29][30][31] 6-Deoxy-6-iodo-L-ascorbic acid (6-IAsA) has been shown to be an effective inhibitor of AsA transport, with tran...

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

Labelled Comp Radiopharmac

Yamamoto

Karasawa

et al. 2009

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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.