Solid tumors often develop an acidic environment due to the Warburg effect. The effectiveness of diagnosis and therapy may therefore be enhanced by the design and use of pH-sensitive agents that target acidic tumors. Recently, a novel technology was introduced to target acidic tumors using pH low insertion peptide (pHLIP), a peptide that inserts across cell membranes as an alpha-helix when the extracellular pH (pH(e)) is acidic.
View Article and Find Full Text PDFThe aim of this work was to prepare a novel class of (64)Cu(II) labeled complexes with the new macrocyclic ligands 1,10-dithia-4,7-diazacyclododecane-3,8-dicarboxylic acid (NEC-SE, 1), 1,10-dithia-4,7-diazacyclotridecane-3,8-dicarboxylic acid (NEC-SP, 2) and 1,10-dithia-4,7-diazacyclotetradecane-3,8-dicarboxylic acid, (NEC-SB, 3 ) to evaluate the usefulness of these macrocycles for potential utility as (64)Cu(II) chelators. The corresponding non-radioactive complexes [Cu(NEC-SE)] x 3H(2)O (4), [Cu(NEC-SP)] x 3H(2)O (5) and [Cu(NEC-SB)] (6) were prepared and their (64)Cu-analogs, [(64)Cu(NEC-SE)] (7) and [(64)Cu(NEC-SP)] (8) and [(64)Cu(NEC-SB)] (9) were produced in >98% radiochemical purity. Rats were injected with complex 7, 8 or 9 and were euthanized at 1, 4 and 24 h.
View Article and Find Full Text PDFBombesin is a tetradecapeptide neurohormone that binds to gastrin-releasing peptide receptors (GRPR). GRPRs have been found in a variety of cancers including invasive breast and prostate tumors. The peptide MP2346 (DOTA-(Pro(1),Tyr(4))-bombesin(1-14)) was designed to bind to these GRP receptors.
View Article and Find Full Text PDFA versatile bifunctional chelating reagent based on a preorganized cyclohexyl derivative of DTPA (CHX-A'') has been developed for the convenient N-terminal labeling of peptides with metal ion radionuclides of Bi(III), In(III), Lu(III), or Y(III). This was achieved via the synthesis of a mono-N-hydroxysuccinimidyl penta-tert-butyl ester derivative of CHX-A'' (trans-cyclohexyldiethylenetriaminepenta-acetic acid) featuring a glutaric acid spacer. Commercially obtained octreotide was modified at its N-terminus by this reagent in the solution phase, and its subsequent radiolabeling with (111)In (T(1/2) = 2.
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