| Sumario: | Purpose: PORPHYSOMES (PS) are multifunctional porphyrin-lipid nanoparticles for fluorescence-guided photochemical tumour ablation and immune stimulation. PS can be radiolabelled with Copper-64 (64Cu-PS) to permit tracing of their whole-body distribution and uptake in tumours with nuclear imaging. Herein we characterised the physicochemical and radiochemical properties of PS and 64Cu-PS and evaluated their pharmacology and toxicology in rats and dogs. Methods: 64Cu-PS labelling procedure was optimised and developed into a "one pot" kit format. The plasma pharmacokinetics (PK), tissue distribution, and single and repeat-dose toxicity of dose escalating PS was evaluated after intravenous injection in healthy Fisher 344 rats and Beagle dogs. Radiation dosimetry from single 64Cu-PS dose was estimated in humans. Results: Kit prepared 64Cu-PS had high labelling yields and mean specific activities of 18.5 MBq/mg (11.4 GBq/mg max). The plasma PK of PS was linear between doses 0.5–15 mg/kg in both rats and dogs. Tissue distribution was primarily to the liver. The estimated effective dose from 64Cu-PS in humans was 38–47 µSv/MBq. Single doses of 32.6 mg/kg PS did not have detectable toxicities in rats. In dogs, mild transient infusion reactions were observed following single and repeat-doses of PS starting at ≥ 10 mg/kg PS. Doses up to 15 mg/kg PS were tolerated in dogs. Conclusions: The pharmacology and safety profiles of PS and 64Cu-PS in rats and dogs did not raise concerns regarding their use in humans. Radiolabelled 64Cu-PS will permit accurate imaging-based assessments of nanoparticle PK and tumour uptake in imaging studies in cancer patients.
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