Clear cell renal cell carcinomas (ccRCC) account for approximately three-quarters of all kidney cancers. When metastatic (mccRCC), their diagnosis and the assessment of their spread are challenging due to the molecular heterogeneity of the tumor. Typically, this evaluation is performed using computed tomography (CT) and scintigraphy, which are highly effective imaging modalities but do not provide information on lymph node invasion.
A radioligand derived from a toxin
A collaboration between teams from LPEM (SIMoS/DMTS) and BioMaps (SHFJ) is exploring the potential of positron emission tomography (PET) as an alternative method. The approach uses a peptide, MQ232, derived from snake venom, which exhibits high in vivo selectivity for the type 2 vasopressin receptor (V2R). V2R is a receptor expressed in the collecting ducts and the distal region of renal tubules. However, it is also ectopically expressed in ccRCC and mccRCC.
MQ232 was chemically synthesized and, in its first version, conjugated to a fluorophore, cyanine 5 (Cy5), to evaluate the peptide’s selectivity and tumor-targeting ability through in vivo fluorescence imaging in mouse models bearing tumors (CHO-V2R).
In a second version, the peptide was radiolabeled with fluorine-18. The metabolic stability and PET pharmacokinetics of [18F]F-MQ232 were evaluated in vivo in mouse models xenografted with human tumor cells derived from ccRCC.
The study shows that:
- [18F]F-MQ232 is highly specific: Its tumor uptake is directly correlated with V2R expression levels in tissues.
- PET/CT imaging performed in xenografted mice shows specific visualization of the tumor compartment with a high tumor-to-background contrast.
- Analysis of human samples confirms the expression of the V2R receptor in clear cell renal cell carcinomas, including metastatic forms.
Published in Theranostics, the study validates the molecular imaging strategy for clear cell renal cell carcinomas based on V2R targeting. It represents a first step toward the development of PET tools for monitoring metastatic spread. Additionally, it highlights the potential of animal venom-derived peptides as a source of new targeting molecules for imaging or theranostic applications.
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This text was translated with the assistance of Mistral AI.