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. 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. 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 2^nd 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. 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 2^nd hour following injection in order to provide sufficiently high integrin specificity.

We present an efficient fully automated sodium [¹⁸F]fluoride radiosynthesis on a new iMiDEV™ cassette-based microfluidic platform.

Due to their very poor prognosis and a fatal outcome, secondary brain tumors are one of the biggest challenges in oncology today. From the point of view of the early diagnosis of these brain micro- and macro-tumors, the sensitivity and specificity of the diagnostic tools constitute an obstacle. Molecular imaging, such as Positron Emission Tomography (PET), is a promising technique but remains limited in the search for cerebral localizations, given the commercially available radiotracers. Indeed, the [¹⁸F]FDG PET remains constrained by the physiological fixation of the cerebral cortex, which hinders the visualization of cerebral metastases. Tumor angiogenesis is recognized as a crucial phenomenon in the progression of malignant tumors and is correlated with overexpression of the neuropilin-1 (NRP-1) receptor. Here, we describe the synthesis and the photophysical properties of the new gallium-68 radiolabeled peptide to target NRP-1. The KDKPPR peptide was coupled with gallium-68 anchored into a bifunctional NODAGA chelating agent, as well as Cy5 for fluorescence detection. The Cy5 absorbance spectra did not change, whereas the molar extinction coefficient (ε) decreased drastically. An enhancement of the fluorescence quantum yield (φ_F) could be observed due to the better water solubility of Cy5. [⁶⁸Ga]Ga-NODAGA-K(Cy5)DKPPR was radiosynthesized efficiently, presented hydrophilic properties (log D = −1.86), and had high in vitro stability (>120 min). The molecular affinity and the cytotoxicity of this new chelated radiotracer were evaluated in vitro on endothelial cells (HUVEC) and MDA-MB-231 cancer cells (hormone-independent and triple-negative line) and in vivo on a brain model of metastasis in a nude rat using the MDA-MB-231 cell line. No in vitro toxicity has been observed. The in vivo preliminary experiments showed promising results, with a high contrast between the healthy brain and metastatic foci for [⁶⁸Ga]Ga-NODAGA-K(Cy5)DKPPR.