Current State and Prospects of Production of Radionuclide Generators for Medical Diagnosis

Pashentsev, V. N.

doi:10.1007/s10527-016-9562-x

Cited by 1 publication

(1 citation statement)

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“…An advantage of using rhenium compounds as anticancer agents is the widespread availability of 99m Tc, an imaging radionuclide that possesses similar chemical properties as rhenium. Complexes of 99m Tc that are structurally analogous to promising rhenium drug candidates can be synthesized and used as in vivo companion diagnostic agents for single-photon emission computed tomography (SPECT) imaging. − To evaluate the potential of a companion imaging agent for Re-9D , we synthesized the analogous radionuclide-based complex of the formula [ 99m Tc( 9D )(CO) 3 (H 2 O)] + ( 99m Tc-9D ( H 2 O )). As described below, our synthetic procedures led to isolation of this aqua-capped species instead of a chlorido-capped compound, which would be more strictly analogous to Re-9D .…”

Section: Resultsmentioning

confidence: 99%

Combinatorial Synthesis to Identify a Potent, Necrosis-Inducing Rhenium Anticancer Agent

et al. 2019

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Combinatorial synthesis can be applied for developing a library of compounds that can be rapidly screened for biological activity. Here, we report the application of microwave-assisted combinatorial chemistry for the synthesis of 80 rhenium(I) tricarbonyl complexes bearing diimine ligands. This library was evaluated for anticancer activity in three different cancer cell lines, enabling the identification of three lead compounds with cancer cell growth-inhibitory activities of less than 10 μM. These three lead structures, Re-9B, Re-9C, and Re-9D, were synthesized independently and fully characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and X-ray crystallography. The most potent of these three complexes, Re-9D, was further explored to understand its mechanism of action. Complex Re-9D is equally effective in both wild-type and cisplatin-resistant A2780 ovarian cancer cells, indicating that it circumvents cisplatin resistance. This compound was also shown to possess promising activity against ovarian cancer tumor spheroids. Additionally, flow cytometry showed that Re-9D does not induce cell cycle arrest or flipping of phosphatidylserine to the outer cell membrane. Analysis of the morphological changes of cancer cells treated with Re-9D revealed that this compound gives rise to rapid plasma membrane rupture. Collectively, these data suggest that Re-9D induces necrosis in cancer cells. To assess the in vivo biodistribution and stability of this compound, a radioactive 99mTc analogue of Re-9D, 99mTc-9D(H2O), was synthesized and administered to naı̈ve BALB/c mice. Results of these studies indicate that 99mTc-9D(H2O) exhibits high metabolic stability and a distinct biodistribution profile. This research demonstrates that combinatorial synthesis is an effective approach for the development of new rhenium anticancer agents with advantageous biological properties.

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Section: Resultsmentioning

confidence: 99%