Dithiol Aryl Arsenic Compounds as Potential Diagnostic and Therapeutic Radiopharmaceuticals

Arsenic-72 (⁷²As) and ⁷⁷As have nuclear properties useful for positron emission tomography (PET) and radiotherapy, respectively. The thiophilic nature of arsenic led to the evaluation of dithioarylarsines for potential use in radiopharmaceuticals. Several dithioarylarsines were synthesized from their arylarsonic acids and dithiols and were fully characterized by NMR, ESI-MS, and X-ray crystallography. This chemistry was translated to the no-carrier-added (nca) ⁷⁷As level. Because arsenic was available at the nca nanomolar level only as [⁷⁷As]­arsenate, this required addition of an aryl group directly to the As to form the [⁷⁷As]­arylarsonic acid. The [⁷⁷As]­arsenate was reduced from ⁷⁷As (V) to ⁷⁷As (III), and a modified Bart reaction was used to incorporate the aryl ring onto the ⁷⁷As, which was followed by dithiol addition. Various modifications and optimizations resulted in 95% radiochemical yield of nca [⁷⁷As]<i>p</i>-ethoxyphenyl-1,2-ethanedithiolatoarsine

Transport of ¹⁸FS and [U-¹⁴C]suc in wild-type and <i>sut1</i> mutant leaves.

<p>A: Photo of leaves collected from two wild-type (WT) and two <i>sut1</i> mutant plants. B: ^<b>18</b>F phosphor image of leaves exposed for one hour to a solution of 200 μCi ^<b>18</b>FS and 125 μCi [^<b>14</b>C]suc. C: ^<b>14</b>C phosphor image obtained after five days exposure.</p

Radiosynthesis of 6’-Deoxy-6’[¹⁸F]Fluorosucrose via Automated Synthesis and Its Utility to Study <i>In Vivo</i> Sucrose Transport in Maize (<i>Zea mays</i>) Leaves

<div><p>Sugars produced from photosynthesis in leaves are transported through the phloem tissues within veins and delivered to non-photosynthetic organs, such as roots, stems, flowers, and seeds, to support their growth and/or storage of carbohydrates. However, because the phloem is located internally within the veins, it is difficult to access and to study the dynamics of sugar transport. Radioactive tracers have been extensively used to study vascular transport in plants and have provided great insights into transport dynamics. To better study sucrose partitioning <i>in vivo</i>, a novel radioactive analog of sucrose was synthesized through a completely chemical synthesis route by substituting fluorine-18 (half-life 110 min) at the 6’ position to generate 6’-deoxy-6’[¹⁸F]fluorosucrose (¹⁸FS). This radiotracer was then used to compare sucrose transport between wild-type maize plants and mutant plants lacking the <i>Sucrose transporter1</i> (<i>Sut1</i>) gene, which has been shown to function in sucrose phloem loading. Our results demonstrate that ¹⁸FS is transported <i>in vivo</i>, with the wild-type plants showing a greater rate of transport down the leaf blade than the <i>sut1</i> mutant plants. A similar transport pattern was also observed for universally labeled [U-¹⁴C]sucrose ([U-¹⁴C]suc). Our findings support the proposed sucrose phloem loading function of the <i>Sut1</i> gene in maize, and additionally demonstrate that the ¹⁸FS analog is a valuable, new tool that offers imaging advantages over [U-¹⁴C]suc for studying phloem transport in plants.</p></div

Transport of ¹⁸F as fluoride in wild-type leaves.

<p>150 μCi of free ^<b>18</b>F was applied to wild-type leaves and allowed to transport for two hours before a one hour image was obtained. Levels close to background were observed in the leaves with very low levels of transport.</p

Internal conversion product of protected precursor.

<p>Internal conversion product of protected precursor.</p

Pertechnetate-Induced Addition of Sulfide in Small Olefinic Acids: Formation of [TcO(dimercaptosuccinate)₂]^5– and [TcO(mercaptosuccinate)₂]^3– Analogues

Technetium-99 (⁹⁹Tc) is important to the nuclear fuel cycle as a long-lived radionuclide produced in ∼6% fission yield from ²³⁵U or ²³⁹Pu. In its most common chemical form, namely, pertechnetate (⁹⁹TcO₄^–), it is environmentally mobile. In situ hydrogen sulfide reduction of pertechnetate has been proposed as a potential method to immobilize environmental ⁹⁹TcO₄^– that has entered the environment. Reactions of ⁹⁹TcO₄^– with sulfide in solution result in the precipitation of Tc₂S₇ except when olefinic acids, specifically fumaric or maleic acid, are present; a water-soluble ⁹⁹Tc species forms. NMR (¹H, ¹³C, and 2D methods) and X-ray absorption spectroscopy [XAS; near-edge (XANES) and extended fine structure (EXAFS)] studies indicate that sulfide adds across the olefinic bond to generate mercaptosuccinic acid (H₃MSA) and/or dimercaptosuccinic acid (H₄DMSA), which then chelate(s) the ⁹⁹Tc to form [⁹⁹TcO­(MSA)₂]^3–, [⁹⁹TcO­(DMSA)₂]^5–, or potentially [⁹⁹TcO­(MSA)­(DMSA)]^4–. 2D NMR methods allowed identification of the products by comparison to ⁹⁹Tc and nonradioactive rhenium standards. The rhenium standards allowed further identification by electrospray ionization mass spectrometry. ⁹⁹TcO₄^– is essential to the reaction because no sulfide addition occurs in its absence, as determined by NMR. Computational studies were performed to investigate the structures and stabilities of the potential products. Because olefinic acid is a component of the naturally occurring humic and fulvic acids found in soils and groundwater, the viability of in situ hydrogen sulfide reduction of environmental ⁹⁹TcO₄^– as an immobilization method is evaluated