Theranostics · 2026
Specific in vivo detection of V2R-positive metastatic ccRCC using a toxin-based PET radioligand.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Petrovic Goran Stanajic, Chmeis Khawla, Gonand Alix, Leguerney Ingrid, Ingels Alexandre, Kereselidze Dimitri, Jego Benoit, Denis Caroline, Urman Apolline, Chaigneau Marion, Baudat Romain, Guyot Antoine, Kessler Pascal, Keck Mathilde, Servent Denis, Richard Mylène, Gilles Nicolas, Truillet Charles
Аннотация
BACKGROUND: The diagnosis of metastatic clear cell renal cell carcinoma (mccRCC) remains challenging due to the tumor's molecular heterogeneity, often resulting in low sensitivity and a high false-positive rate. In this study, we introduce and validate a new imaging modality for mccRCC based on the first radioligand targeting the type 2 vasopressin receptor (V2R) suitable for positron emission tomography (PET). V2R is ectopically expressed in mccRCC. This imaging approach utilizes [18F]F-MQ232, a radiolabeled peptide derived from snake venom which exhibits high in vivo selectivity for V2R.
METHODS: The V2R-selective peptide MQ232 conjugated with either a cyanine 5 (Cy5) or a fluorine 18 (18F) group were chemically synthetized. V2R mRNA was quantified and protein expression assessed by flow cytometry using Cy5-MQ232. The selectivity and tumor targeting ability of the modified MQ232 peptides were assessed using in vivo fluorescence imagery in tumor-bearing mice using CHO-V2R tumors with graded expression. Metabolic stability and PET pharmacokinetics of [18F]F-MQ232 were assessed in rodents. Specific tumor targeting and imaging contrast were validated in vivo using V2R-expressing tumors.
RESULTS: [18F]F-MQ232 is a highly relevant radioligand whose tumor uptake directly correlates with V2R expression levels in tissues, demonstrating its specificity to V2R-expressing tumors. Replacing the peptide moiety by an isoform unable to interact with V2R leads to a drastic decrease in the radioligand's tumor uptake, highlighting its origin in a specific, ligand/receptor type interaction between the MQ232 moiety and V2R. PET/CT imaging of Caki-1 xenografted mice demonstrated the ability of [18F]F-MQ232 to allow specific detection of the tumor compartment associated with high tumor-to-background contrast. RT-qPCR screening of metastatic and non-metastatic ccRCC biopsies from patients confirms V2R expression.
CONCLUSIONS: This work validates the V2R-targeting strategy in mccRCC using [18F]F-MQ232 and demonstrates that human mccRCC tissues express V2R, confirming the suitability of this specific imaging technique for metastasis extension assessment.
METHODS: The V2R-selective peptide MQ232 conjugated with either a cyanine 5 (Cy5) or a fluorine 18 (18F) group were chemically synthetized. V2R mRNA was quantified and protein expression assessed by flow cytometry using Cy5-MQ232. The selectivity and tumor targeting ability of the modified MQ232 peptides were assessed using in vivo fluorescence imagery in tumor-bearing mice using CHO-V2R tumors with graded expression. Metabolic stability and PET pharmacokinetics of [18F]F-MQ232 were assessed in rodents. Specific tumor targeting and imaging contrast were validated in vivo using V2R-expressing tumors.
RESULTS: [18F]F-MQ232 is a highly relevant radioligand whose tumor uptake directly correlates with V2R expression levels in tissues, demonstrating its specificity to V2R-expressing tumors. Replacing the peptide moiety by an isoform unable to interact with V2R leads to a drastic decrease in the radioligand's tumor uptake, highlighting its origin in a specific, ligand/receptor type interaction between the MQ232 moiety and V2R. PET/CT imaging of Caki-1 xenografted mice demonstrated the ability of [18F]F-MQ232 to allow specific detection of the tumor compartment associated with high tumor-to-background contrast. RT-qPCR screening of metastatic and non-metastatic ccRCC biopsies from patients confirms V2R expression.
CONCLUSIONS: This work validates the V2R-targeting strategy in mccRCC using [18F]F-MQ232 and demonstrates that human mccRCC tissues express V2R, confirming the suitability of this specific imaging technique for metastasis extension assessment.