Details

Autor(en) / Beteiligte

• Isal, Sibel
• Pierson, Julien
• Imbert, Laetitia
• Clement, Alexandra
• Collet, Charlotte
• Pinel, Sophie
• Veran, Nicolas
• Reinhard, Aurélie
• Poussier, Sylvain
• Gauchotte, Guillaume
• Frezier, Steeven
• Karcher, Gilles
• Marie, Pierre-Yves
• Maskali, Fatiha

Titel

PET imaging of 68Ga-NODAGA-RGD, as compared with 18F-fluorodeoxyglucose, in experimental rodent models of engrafted glioblastoma

Ist Teil von

• EJNMMI research, 2018-06, Vol.8 (1), p.1-9, Article 51

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Background Tracers triggering αvβ3 integrins, such as certain RGD-containing peptides, were found promising in previous pilot studies characterizing high-grade gliomas. However, only limited comparisons have been performed with current PET tracers. This study aimed at comparing the biodistribution of 18 F-fluorodeoxyglucose ( 18 F-FDG) with that of 68 Ga-NODAGA-RGD, an easily synthesized monomeric RGD compound with rapid kinetics, in two different rodent models of engrafted human glioblastoma. Methods Nude rodents bearing human U87-MG glioblastoma tumor xenografts in the flank (34 tumors in mice) or in the brain (5 tumors in rats) were analyzed. Kinetics of 68 Ga-NODAGA-RGD and of 18 F-FDG were compared with PET imaging in the same animals, along with additional autohistoradiographic analyses and blocking tests for 68 Ga-NODAGA-RGD. Results Both tracers showed a primary renal route of clearance, although with faster clearance for 68 Ga-NODAGA-RGD resulting in higher activities in the kidneys and bladder. The tumor activity from 68 Ga-NODAGA-RGD, likely corresponding to true integrin binding (i.e., suppressed by co-injection of a saturating excess of unlabeled RGD), was found relatively high, but only at the 2 nd hour following injection, corresponding on average to 53% of total tumor activity. Tumor uptake of 68 Ga-NODAGA-RGD decreased progressively with time, contrary to that of 18 F-FDG, although 68 Ga-NODAGA-RGD exhibited 3.4 and 3.7-fold higher tumor-to-normal brain ratios on average compared to 18 F-FDG in mice and rat models, respectively. Finally, ex-vivo analyses revealed that the tumor areas with high 68 Ga-NODAGA-RGD uptake also exhibited the highest rates of cell proliferation and αv integrin expression, irrespective of cell density. Conclusions 68 Ga-NODAGA-RGD has a high potential for PET imaging of glioblastomas, especially for areas with high integrin expression and cell proliferation, although PET recording needs to be delayed until the 2 nd hour following injection in order to provide sufficiently high integrin specificity.