TY - JOUR

T1 - PET imaging of liposomes labeled with an [¹⁸F]-fluorocholesteryl ether probe prepared by automated radiosynthesis

AU - Jensen, Andreas Tue Ingemann

AU - Binderup, Tina

AU - Andresen, Thomas L

AU - Kjær, Andreas

AU - Rasmussen, Palle

PY - 2012/12

Y1 - 2012/12

N2 - A novel [¹⁸F]-labeled cholesteryl ether lipid probe was prepared by synthesis of the corresponding mesylate, which was [¹⁸F]-fluorinated by a [¹⁸F]KF, Kryptofix-222, K₂CO₃ procedure. Fluorination was done for 10 minutes at 165°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 [¹⁸F]-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 [¹⁸F]-labeled liposomes could be suitable as a methodology for visualization of tumors and obtaining short-term pharmacokinetics in vivo.

AB - A novel [¹⁸F]-labeled cholesteryl ether lipid probe was prepared by synthesis of the corresponding mesylate, which was [¹⁸F]-fluorinated by a [¹⁸F]KF, Kryptofix-222, K₂CO₃ procedure. Fluorination was done for 10 minutes at 165°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 [¹⁸F]-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 [¹⁸F]-labeled liposomes could be suitable as a methodology for visualization of tumors and obtaining short-term pharmacokinetics in vivo.

U2 - 10.3109/08982104.2012.698418

DO - 10.3109/08982104.2012.698418

M3 - Journal article

C2 - 22803638

VL - 22

SP - 295

EP - 305

JO - Journal of Liposome Research

JF - Journal of Liposome Research

SN - 0898-2104

IS - 4

ER -