%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