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Abstract #3883

Biological Modifiers of Novel Theranostic Metalloporphyrins

Talaignair N. Venkatraman1, Artek Tovmasyan2, Ines Batinic-Haberle2, Ivan Spasojevic2, Christopher D. Lascola1

1Radiology, Duke University Medical Center, Durham, NC, United States; 2Radiation Oncology, Duke University Medical Center, Durham, NC, United States

This study investigates the potential impact of common biological moieties on the relaxation properties of our two lead candidate MnPs (MnTE-2-PyP5+ and MnTnHex-2-PyP5+). These include the most abundant intracellular redox mediator, ascorbate; (2) the most metabolically relevant counter-anion, citrate; (3) and the most abundant serum protein, albumin. With respect to likely biological redox modifiers, both MnP isoforms showed a systematic reduction in relaxivity in the presence of ascorbate, consistent with the hypothesis that metal center oxidation state will have a significant impact on relaxation properties of MnPs in vivo. Intriguingly, citrate anion does not negatively impact relaxation, and in the case of MnTE2PyP5+, may actually enhance contrast enhancement. These two isoforms of MnP demonstrate impressive relaxation properties that enable MR detection in vivo.

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Keywords

abundant acid actions active activity actually agents albumin although anion appear assessments association binding biological candidate carried central characterization chem chemotherapeutics citrate citric class coil common compete complex compound concentration consistent contrast counter cycling decreases described detection developed diagnostic diluted diseased duke dynamic enable enhance enhancement essential examined exchange facilitate form free future human hypothesis impact impressive improved in vivo include independent indicators influence inner instead interpretation intracellular intriguingly investigated investigates keeping lead likely limited longitudinal manganese maps markedly materials matrix measured mechanism mediator medical metabolically metal modifiers moieties molecular negatively novel oncology otherwise oxidation paramagnetic phantoms poor possibly post potential powerful prepared presence previous previously probes processed properties protein quadrature quantitative radiation radical radiology recently recovery reduction regardless relevant remained rendering respect saturation selective serum solubility sphere status stock structure subtle summarizes system systematic table therapeutic therapeutically tissue tissues toxicity trans translation transverse underlying virtually volume water weak