Improved PET imaging of tumors in mice using a novel (18) F-folate conjugate with an albumin-binding entity
Autor: | Cristina Müller, Viola Groehn, Simon M. Ametamey, Cindy R. Fischer, Roger Schibli, Josefine Reber |
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Rok vydání: | 2013 |
Předmět: |
Cancer Research
Biodistribution Mice Nude Mice Folic Acid In vivo Fluorodeoxyglucose F18 Albumins Cell Line Tumor Neoplasms Medicine Animals Humans Radiology Nuclear Medicine and imaging Tissue Distribution medicine.diagnostic_test business.industry Radiosynthesis Molecular biology In vitro Oncology Biochemistry Folate receptor Positron emission tomography Positron-Emission Tomography Specific activity Female Radiopharmaceuticals business Conjugate |
Zdroj: | Molecular imaging and biology. 15(6) |
ISSN: | 1860-2002 |
Popis: | The folate receptor (FR) is a promising target for nuclear imaging due to its overexpression in many different cancer types. A drawback of using folate radioconjugates is the high accumulation of radioactivity in the kidneys. Therefore, the aim of this study was to develop a (18) F-labeled folate conjugate with an albumin-binding entity to enhance the blood circulation time and hence improve the tumor-to-kidney ratio.The novel (18) F-folate was prepared by conjugation of a (18) F-labeled glucose azide to an alkyne-functionalized folate precursor containing an albumin-binding entity via Cu(I)-catalyzed 1,3-dipolar cycloaddition. The radioconjugate was tested in vitro on FR-positive KB tumor cells and by biodistribution and positron emission tomography (PET) imaging studies using KB tumor-bearing mice.The radiosynthesis of the albumin-binding [(18) F]fluorodeoxyglucose-folate ([(18) F]3) resulted in a radiochemical yield of 1-2 % decay corrected (d.c.) and a radiochemical purity of ≥95 %. The specific activity of [(18) F]3 ranged from 20 to 50 GBq/μmol. In vitro experiments revealed FR-specific binding of [(18) F]3 to KB tumor cells. In vivo we found an increasing uptake of [(18) F]3 into tumor xenografts over time reaching a value of ∼ 15 % injected dose (ID)/g at 4 h post-injection (p.i.). Uptake in the kidneys (∼ 13 % ID/g; 1 h p.i.) was approximately fourfold reduced compared to previously published (18) F-labeled folic acid derivatives. An excellent visualization of tumor xenografts with an unprecedentedly high tumor-to-kidney ratio (∼ 1) was obtained by PET imaging.[(18) F]3 showed a favorable accumulation in tumor xenografts compared to the same folate conjugate without albumin-binding properties. Moreover, the increased tumor-to-kidney ratios improved the PET imaging quality significantly, in spite of a somewhat higher background radioactivity which was a consequence of the slower blood clearance of [(18) F]3. |
Databáze: | OpenAIRE |
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