| In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel 99mTc-radiofolate tracer. | |
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MedLine Citation:
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PMID: 16721570 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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) 4 h 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. |
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Authors:
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Cristina Müller; P August Schubiger; Roger Schibli |
Publication Detail:
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Type: Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't Date: 2006-05-24 |
Journal Detail:
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Title: European journal of nuclear medicine and molecular imaging Volume: 33 ISSN: 1619-7070 ISO Abbreviation: Eur. J. Nucl. Med. Mol. Imaging Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-29 Completed Date: 2007-05-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101140988 Medline TA: Eur J Nucl Med Mol Imaging Country: Germany |
Other Details:
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Languages: eng Pagination: 1162-70 Citation Subset: IM |
Affiliation:
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Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carrier Proteins / metabolism* Cell Line, Tumor Drug Delivery Systems / methods Folic Acid / diagnostic use*, pharmacokinetics* Humans Metabolic Clearance Rate Mice Molecular Probe Techniques Neoplasms / metabolism*, radionuclide imaging* Organ Specificity Radiopharmaceuticals / diagnostic use, pharmacokinetics Receptors, Cell Surface / metabolism* Technetium / diagnostic use*, pharmacokinetics* Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Radiopharmaceuticals; 0/Receptors, Cell Surface; 0/folate-binding protein; 59-30-3/Folic Acid; 7440-26-8/Technetium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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