Development and initial evaluation of novel fluorine-18 labeled nanocarrier "Lactosome" as a tumor imaging probe for PET

Objectives We have developed amphiphilic polydepsipeptide micelle "Lactosome" as a novel nanocarrier with tumor accumulation property by the enhanced permeability and retention effect for cancer imaging probes. We reported previously that a near infrared fluorescent (NIRF) imaging of mouse tumor with using ICG-lactosome. In this study, with aim of developing radiotracers for in vivo tumor imaging by PET, ¹⁸F-lactosome was synthesized and evaluated.

Methods As a containable molecule into the lactosome, ¹⁸F labeled polylactic acid (¹⁸F-BzPLA) was synthesized in 20-37 % EOB by coupling reaction of SFB connected at an amino group terminal of polylactic acid. Micelle assemblies were prepared from a mixture of ¹⁸F-BzPLA and the amphiphilic polymer by a film method. For biodistribution studies, BALB/cA Jcl-nu/nu mice bearing HeLa cells in femur region were used. We took images by both PET and NIRF images of tumor bearing mice after co-injected ¹⁸F-lactosome with ICG-lactosome by using both Clairvivo PET and Clairvivo OPT (Shimadzu Corp. Japan) respectively.

Results ¹⁸F-Lactosome was prepared in good yields (222-420 MBq). The radioactivity of ¹⁸F-lactosome was found to be stable in a blood circulation and maintained to higher level during 10 min to 6 hrs after injection. Tumor uptake increased gradually after injection. The mean uptake ratios of tumor/muscle, tumor/digestive tract and tumor/brain were 2.7, 2.8 and 4.9 at 6 hrs. In addition, tumor PET imaging of ¹⁸F-lactosome was capable and similar to NIRF imaging by ICG-lactosome.

Conclusions Tumor imaging by PET with using lactosome as a nanocarrier is therefore a potential candidate for a facile and general tumor imaging technique