In vivo evaluation of PEGylated 64Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

Purpose

The objective of this study was to evaluate the potential of PEGylated ⁶⁴Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated ¹⁷⁷Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model.

Methods

Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and ⁶⁴Cu- and ¹⁷⁷Lu-loading efficiency. The tumor imaging potential of ⁶⁴Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The ⁶⁴Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of ¹⁷⁷Lu-liposomes.

Results

High remote loading efficiency (>95 %) was obtained for both ⁶⁴Cu and ¹⁷⁷Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 °C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2?±?0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the ⁶⁴Cu-liposomes estimated an acceptable total effective dose of 3.3·10^?2 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic ¹⁷⁷Lu-liposomes.

Conclusion

The overall preclinical profile of PEGylated ⁶⁴Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of ⁶⁴Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated ⁶⁴Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for ¹⁷⁷Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of ¹⁷⁷Lu-liposomes in animals before potential testing in man.