DOI: 10.1186/s13550-018-0405-5Pages: 1-9

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

1. CHRU-Nancy, Department of Nuclear Medicine

2. CHRU-Nancy, Lorraine University, Nancyclotep Molecular and Experimental Imaging Platform

3. Lorraine University, INSERM, IADI, UMR 1254

4. Lorraine University, CNRS, CRAN, UMR 7039

5. CHRU-Nancy, Université de Lorraine, Department of Pathology

6. Lorraine University, INSERM, NGERE, UMR 954

7. Lorraine University, INSERM, DCAC, UMR 1116

8. Nancyclotep Molecular and Experimental Imaging Platform, POSIFIT

Correspondence to:
Fatiha Maskali
Tel: (33) 3 83 15 79 58
Email: f.maskali@nancyclotep.com

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Abstract

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 18F-fluorodeoxyglucose (18F-FDG) with that of 68Ga-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 68Ga-NODAGA-RGD and of 18F-FDG were compared with PET imaging in the same animals, along with additional autohistoradiographic analyses and blocking tests for 68Ga-NODAGA-RGD.

Results

Both tracers showed a primary renal route of clearance, although with faster clearance for 68Ga-NODAGA-RGD resulting in higher activities in the kidneys and bladder. The tumor activity from 68Ga-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 2nd hour following injection, corresponding on average to 53% of total tumor activity. Tumor uptake of 68Ga-NODAGA-RGD decreased progressively with time, contrary to that of 18F-FDG, although 68Ga-NODAGA-RGD exhibited 3.4 and 3.7-fold higher tumor-to-normal brain ratios on average compared to 18F-FDG in mice and rat models, respectively. Finally, ex-vivo analyses revealed that the tumor areas with high 68Ga-NODAGA-RGD uptake also exhibited the highest rates of cell proliferation and αv integrin expression, irrespective of cell density.

Conclusions

68Ga-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 2nd hour following injection in order to provide sufficiently high integrin specificity.

This article is freely available, click here to access the full text/PDF

  • Accepted: Jun 1, 2018
  • Online: Jun 15, 2018

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