Journal article
PET imaging of liposomes labeled with an [18F]-fluorocholesteryl ether probe prepared by automated radiosynthesis
Department of Micro- and Nanotechnology, Technical University of Denmark1
Center for Nuclear Technologies, Technical University of Denmark2
The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark3
Copenhagen University Hospital Herlev and Gentofte4
Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark5
A novel [F-18]-labeled cholesteryl ether lipid probe was prepared by synthesis of the corresponding mesylate, which was [F-18]-fluorinated by a [F-18]KF, Kryptofix-222, K2CO3 procedure. Fluorination was done for 10 minutes at 165 degrees C and took place with conversion between 3 and 17%, depending on conditions.
Radiolabelling of the probe and subsequent in situ purification on SEP-Paks were done on a custom-built, fully automatic synthesis robot. Long-circulating liposomes were prepared by hydration (magnetic stirring) of a lipid film containing the radiolabeled probe, followed by fully automated extrusion through 100-nm filters.
The [F-18]-labeled liposomes were injected into nude, tumor-bearing mice, and positron emission tomography (PET) scans were performed several times over 8 hours to investigate the in vivo biodistribution. Clear tumor accumulation, as well as hepatic and splenic uptake, was observed, corresponding to expected liposomal pharmacokinetics.
The tumor accumulation 8 hours postinjection accounted for 2.25 +/- 0.23 (mean +/- standard error of the mean) percent of injected dose per gram (%ID/g), and the tumor-to-muscle ratio reached 2.20 +/- 0.24 after 8 hours, which is satisfactorily high for visualization of pathological lesions. Moreover, the blood concentration was still at a high level (13.9 +/- 1.5 %ID/g) at the end of the 8-hour time frame.
The present work demonstrates the methodology for automated preparation of radiolabeled liposomes, and shows that [F-18]-labeled liposomes could be suitable as a methodology for visualization of tumors and obtaining short-term pharmacokinetics in vivo.
| Language: | English |
|---|---|
| Publisher: | Taylor & Francis |
| Year: | 2012 |
| Pages: | 295-305 |
| ISSN: | 15322394 and 08982104 |
| Types: | Journal article |
| DOI: | 10.3109/08982104.2012.698418 |
| ORCIDs: | Jensen, Andreas Tue Ingemann , Andresen, Thomas Lars and 0000-0002-2706-5547 |
10-cholesteryloxy-1-[fluorine-18]fluoro-decanol diagnostic-drug pharmacokinetics 10511, Biophysics - Bioengineering 12504, Pathology - Diagnostic 12512, Pathology - Therapy 14004, Digestive system - Physiology and biochemistry 15002, Blood - Blood and lymph studies 15004, Blood - Blood cell studies 22002, Pharmacology - General 24003, Neoplasms - Immunology 24004, Neoplasms - Pathology, clinical aspects and systemic effects 34502, Immunology - General and methods 34508, Immunology - Immunopathology, tissue immunology Biomaterials Kryptofix-222 23978-09-8 Methods and Techniques Pharmaceuticals Pharmacology Rodentia Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Rodents, Vertebrates) - Muridae [86375] mouse common Tumor Biology [fluorine-18]-fluorocholesteryl ether probe automated radiosynthesis method laboratory techniques custom-built fully automatic synthesis robot laboratory equipment fluorine-18-labeled cholesteryl ether diagnostic-drug pharmacokinetics liposome liver digestive system magnetic stirring method laboratory techniques positron emission tomography imaging PET imaging imaging and microscopy techniques, diagnostic techniques potassium carbonate 584-08-7 spleen immune system, blood and lymphatics tumor Neoplasms (MeSH) neoplastic disease
