Preliminary Study of New Gallium-68 Radiolabeled Peptide Targeting NRP-1 to Detect Brain Metastases by Positron Emission Tomography

Abstract

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 (φF) 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.

Aerosol–Cell Exposure System Applied to Semi-Adherent Cells for Aerosolization of Lung Surfactant and Nanoparticles Followed by High Quality RNA Extraction

“…Predictably, this list has been growing since 2005, in all areas of production, leading to serious concerns regarding the effects of their exposure on human health [1][2][3]. Moreover, the emergence of nanotechnologies has led to the development of new research fields such as nanomedicine, which focuses on the synthesis and engineering of nanomaterials for drug delivery [4], which has led to novel treatment [5][6][7][8] and diagnostic options [9,10] and combinations thereof [11,12]. Consequently, the study of both adverse and therapeutic health effects of nanoparticles and new nanomaterials is a crucial issue for the development of safe nano-enabled products such as consumer products as well as medical products.…”

Preparation and bioevaluation of [99mTc]Tc-labeled A7R and DA7R for SPECT imaging of triple-negative breast cancer

“…13–15 Therefore, VEGFR2 and NRP-1 have been identified as targets for the development of various imaging agents for tumor detection, providing novel strategies for TNBC diagnosis. 16,17…”

“…[13][14][15] Therefore, VEGFR2 and NRP-1 have been identified as targets for the development of various imaging agents for tumor detection, providing novel strategies for TNBC diagnosis. 16,17 A homing peptide-based active targeting system is an effective approach for delivering payloads such as imaging agents or drugs to diseased tissues. 18,19 An increasing number of homing peptides for the diagnosis and treatment of tumors have been explored, such as iRGD, LyP-1, PL3, and Angiopep-2.…”