%0 Journal Article %A Imberti, Cinzia %A Y. A. Terry, Samantha %A Cullinane, Carleen %A Clarke, Fiona %A H. Cornish, Georgina %A Ramakrishnan, Nisha K. %A Roselt, Peter %A P. Cope, Andrew %A Hicks, Rodney J. %A Blower, Philip J. %A Ma, Michelle T. %D 2016 %T Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of αvβ3 Integrin Expression with Gallium-68 %U https://acs.figshare.com/articles/journal_contribution/Enhancing_PET_Signal_at_Target_Tissue_in_Vivo_Dendritic_and_Multimeric_Tris_hydroxypyridinone_Conjugates_for_Molecular_Imaging_of_sub_v_sub_sub_3_sub_Integrin_Expression_with_Gallium-68/4315859 %R 10.1021/acs.bioconjchem.6b00621.s001 %2 https://acs.figshare.com/ndownloader/files/7039334 %K receptor-mediated tumor uptake %K RGD 3 %K nontarget organ retention %K trimeric peptide homologue %K dendritic bifunctional chelator %K Ga %K homologues HP 3 %K positron-emitting isotope gallium -68 %K SCN-HP %K α v β 3 integrin receptor %K exhibits receptor-mediated uptake %K α v β 3 integrin receptor expression %K nontarget organ contrast %K biodistribution studies show %K peptide receptor expression %K α v β 3 Integrin Expression %K U 87MG tumors %K Enhancing PET Signal %K overexpress α v β 3 integrin %K metal binding site %X Tris­(hydroxypyridinone) chelators conjugated to peptides can rapidly complex the positron-emitting isotope gallium-68 (68Ga) under mild conditions, and the resulting radiotracers can delineate peptide receptor expression at sites of diseased tissue in vivo. We have synthesized a dendritic bifunctional chelator containing nine 1,6-dimethyl-3-hydroxypyridin-4-one groups (SCN-HP9) that can coordinate up to three Ga3+ ions. This derivative has been conjugated to a trimeric peptide (RGD3) containing three peptide groups that target the αvβ3 integrin receptor. The resulting dendritic compound, HP9-RGD3, can be radiolabeled in 97% radiochemical yield at a 3-fold higher specific activity than its homologues HP3-RGD and HP3-RGD3 that contain only a single metal binding site. PET scanning and biodistribution studies show that [68Ga­(HP9-RGD3)] demonstrates higher receptor-mediated tumor uptake in animals bearing U87MG tumors that overexpress αvβ3 integrin than [68Ga­(HP3-RGD)] and [68Ga­(HP3-RGD3)]. However, concomitant nontarget organ retention of [68Ga­(HP9-RGD3)] results in low tumor to nontarget organ contrast in PET images. On the other hand, the trimeric peptide homologue containing a single tris­(hydroxypyridinone) chelator, [68Ga­(HP3-RGD3)], clears nontarget organs and exhibits receptor-mediated uptake in mice bearing tumors and in mice with induced rheumatoid arthritis. PET imaging with [68Ga­(HP3-RGD3)] enables clear delineation of αvβ3 integrin receptor expression in vivo. %I ACS Publications