In vivo Evaluation of PEGylated ⁶⁴Cu-liposomes with Theranostic and Radiotherapeutic Potential using Micro PET/CT

The objective of this study was to evaluate the potentialof PEGylated 64Cu-liposomes in clinical diagnosticpositron emission tomography (PET) imaging andPEGylated 177Lu-liposomes in internal tumor radiotherapythrough in vivo characterization and dosimetric analysis in ahuman xenograft mouse model. Liposomes with 5 and 10 mol% PEG were characterizedwith respect to size, charge, and 64Cu- and 177Lu-loadingefficiency. The tumor imaging potential of 64Cu-loadedliposomes was evaluated in terms of in vivo biodistribution,tumor accumulation and tumor-to-muscle (T/M) ratios, usingPET imaging. The potential of PEGylated liposomes for diagnosticand therapeutic applications was further evaluatedthrough dosimetry analysis using OLINDA/EXM software.The 64Cu-liposomes were used as biological surrogates toestimate the organ and tumor kinetics of 177Lu-liposomes.High remote loading efficiency (>95 %) was obtainedfor both 64Cu and 177Lu radionuclides with PEGylated liposomes,and essentially no leakage of the encapsulated radionuclidewas observed upon storage and after serum incubationfor 24 h at 37 °C. The 10 mol% PEG liposomes showedhigher tumor accumulation (6.2±0.2 %ID/g) than the 5mol% PEG liposomes, as evaluated by PET imaging. Thedosimetry analysis of the 64Cu-liposomes estimated an acceptabletotal effective dose of 3.3·10−2 mSv/MBq for diagnosticimaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic 177Luliposomes. The overall preclinical profile of PEGylated64Cu-liposomes showed high potential as a new PETtheranostic tracer for imaging in humans. Dosimetry resultspredicted that initial administered activity of 200 MBq of64Cu-liposomes should be acceptable in patients. Work is inprogress to validate the utility of PEGylated 64Cu-liposomesin a clinical research programme. The high absorbed tumordose (114 mGy/MBq) estimated for 177Lu-liposomes and thepreliminary dosimetric studies justify further therapeutic anddosimetry investigation of 177Lu-liposomes in animals beforepotential testing in man.