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In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel 99mTc-radiofolate tracer

Müller, Cristina ; Schubiger, P. ; Schibli, Roger

In: European Journal of Nuclear Medicine and Molecular Imaging, 2006, vol. 33, no. 10, p. 1162-1170

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    Titel
    • In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel 99mTc-radiofolate tracer
    Autor
    • Müller, Cristina. Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
    • Schubiger, P.. Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
    • Schibli, Roger. Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • European Journal of Nuclear Medicine and Molecular Imaging, 2006, vol. 33, no. 10, p. 1162-1170. Springer-Verlag
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:311882
    Summary
    Purpose: For the assessment of folate-based radiopharmaceuticals, human nasopharyngeal KB carcinoma cells are traditionally used although nasopharyngeal cancer is rare. On the other hand, the folate receptor (FR) is frequently overexpressed on diverse cancer types, the highest frequency (>90%) being on ovarian carcinomas. The goal of our study was the in vitro and in vivo assessment of different FR-positive human carcinoma cells. In addition, a murine sarcoma cell line was assessed as a pre-clinical alternative to human xenograft models. Methods: FR-positive human nasopharyngeal, cervical, ovarian and colorectal cancer cell lines and the transgenic mouse sarcoma (24JK-FBP) cell line were targeted with a novel 99mTc-tricarbonyl folate derivative 2. Comparative in vitro cell binding studies were carried out under standardised folate-deficient conditions. In vivo studies were performed in nude mice and C6 black mice. Results: The in vitro cell experiments revealed only FR-specific binding (unspecific <0.02%), ranging from 3.5% to 52% of complex 2 owing to variable levels of FR expression of the cell lines. In vivo tumour uptake of radiotracer 2 varied less than in vitro. It ranged from 0.66±0.17% ID/g (LoVo) through 1.16±0.64%ID/g (IGROV-1) and 1.55±0.43% ID/g (24JK-FBP) to 2.33±0.36% ID/g (KB) 4h p.i. Conclusion: These pre-clinical studies indicate that in vitro data obtained in FR-positive cancer cells do not necessarily correspond with or predict in vivo radiofolate uptake in corresponding (xeno)grafts. In addition, the murine 24JK-FBP cell line proved to be a valuable pre-clinical alternative to human tumour models