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Tris(hydroxypyridinone) chelators conjugated to peptides can rapidly complex the positron-emitting isotope gallium-68 ( 68 Ga) 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-HP 9 ) that can coordinate up to three Ga 3+ ions. This derivative has been conjugated to a trimeric peptide (RGD 3 ) containing three peptide groups that target the α v β 3 integrin receptor. The resulting dendritic compound, HP 9 -RGD 3 , can be radiolabeled in 97% radiochemical yield at a 3-fold higher specific activity than its homologues HP 3 -RGD and HP 3 -RGD 3 that contain only a single metal binding site. PET scanning and biodistribution studies show that [ 68 Ga(HP 9 -RGD 3 )] demonstrates higher receptor-mediated tumor uptake in animals bearing U87MG tumors that overexpress α v β 3 integrin than [ 68 Ga(HP 3 -RGD)] and [ 68 Ga(HP 3 -RGD 3 )]. However, concomitant nontarget organ retention of [ 68 Ga(HP 9 -RGD 3 )] 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, [ 68 Ga(HP 3 -RGD 3 )], clears nontarget organs and exhibits receptor-mediated uptake in mice bearing tumors and in mice with induced rheumatoid arthritis. PET imaging with [ 68 Ga(HP 3 -RGD 3 )] enables clear delineation of α v β 3 integrin receptor expression in vivo.

bioconjugate chemistry

Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of α<sub>v</sub>β<sub>3</sub> Integrin Expression with Gallium-68

Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of αvβ3 Integrin Expression with Gallium-68

Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of α_vβ₃ Integrin Expression with Gallium-68