TY - JOUR
T1 - Novel Peptide-Based PET Probe for Non-invasive Imaging of C-X-C Chemokine Receptor Type 4 (CXCR4) in Tumors
AU - Trotta, Anna Maria
AU - Aurilio, Michela
AU - D'Alterio, Crescenzo
AU - Ieranò, Caterina
AU - Di Martino, Daria
AU - Barbieri, Antonio
AU - Luciano, Antonio
AU - Gaballo, Paolo
AU - Santagata, Sara
AU - Portella, Luigi
AU - Tomassi, Stefano
AU - Marinelli, Luciana
AU - Sementa, Deborah
AU - Novellino, Ettore
AU - Lastoria, Secondo
AU - Scala, Stefania
AU - Schottelius, Margret
AU - Di Maro, Salvatore
N1 - Funding Information:
This research was funded by the Italian Ministry of Health (RF-2018-12367026), EraNet-Euro-Nanomed 2: Target4Cancer 2015, the Italian Ministry of Education, University and Research Progetti di Rilevante Interesse Nazionale (PRIN) 2017 (2017PHRC8X_004, to S.D.M. and L.M.), and the Campania Regional Government Technology Platform Lotta alle Patologie Oncologiche (iCURE to S.D.M.). Moreover, S.T. acknowledges MIUR-Ministero dell’Istruzione, dell’Università e della Ricerca (Italian Ministry of Education, University and Research), PON R&I 2014-2020-AIM (Attraction and International Mobility), Project AIM1873131-2, linea 1.
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021
Y1 - 2021
N2 - The recently reported CXCR4 antagonist 3 (Ac-Arg-Ala-[DCys-Arg-2Nal-His-Pen]-CO2H) was investigated as a molecular scaffold for a CXCR4-targeted positron emission tomography (PET) tracer. Toward this end, 3 was functionalized with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononanetriacetic acid (NOTA). On the basis of convincing affinity data, both tracers, [68Ga]NOTA analogue ([68Ga]-5) and [68Ga]DOTA analogue ([68Ga]-4), were evaluated for PET imaging in "in vivo"models of CHO-hCXCR4 and Daudi lymphoma cells. PET imaging and biodistribution studies revealed higher CXCR4-specific tumor uptake and high tumor/background ratios for the [68Ga]NOTA analogue ([68Ga]-5) than for the [68Ga]DOTA analogue ([68Ga]-4) in both in vivo models. Moreover, [68Ga]-4 and [68Ga]-5 displayed rapid clearance and very low levels of accumulation in all nontarget tissues but the kidney. Although the high tumor/background ratios observed in the mouse xenograft model could partially derive from the hCXCR4 selectivity of [68Ga]-5, our results encourage its translation into a clinical context as a novel peptide-based tracer for imaging of CXCR4-overexpressing tumors.
AB - The recently reported CXCR4 antagonist 3 (Ac-Arg-Ala-[DCys-Arg-2Nal-His-Pen]-CO2H) was investigated as a molecular scaffold for a CXCR4-targeted positron emission tomography (PET) tracer. Toward this end, 3 was functionalized with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononanetriacetic acid (NOTA). On the basis of convincing affinity data, both tracers, [68Ga]NOTA analogue ([68Ga]-5) and [68Ga]DOTA analogue ([68Ga]-4), were evaluated for PET imaging in "in vivo"models of CHO-hCXCR4 and Daudi lymphoma cells. PET imaging and biodistribution studies revealed higher CXCR4-specific tumor uptake and high tumor/background ratios for the [68Ga]NOTA analogue ([68Ga]-5) than for the [68Ga]DOTA analogue ([68Ga]-4) in both in vivo models. Moreover, [68Ga]-4 and [68Ga]-5 displayed rapid clearance and very low levels of accumulation in all nontarget tissues but the kidney. Although the high tumor/background ratios observed in the mouse xenograft model could partially derive from the hCXCR4 selectivity of [68Ga]-5, our results encourage its translation into a clinical context as a novel peptide-based tracer for imaging of CXCR4-overexpressing tumors.
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U2 - 10.1021/acs.jmedchem.1c00066
DO - 10.1021/acs.jmedchem.1c00066
M3 - Article
C2 - 33660512
AN - SCOPUS:85103440490
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
ER -