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Purpose <p>PORPHYSOMES (PS) are multifunctional porphyrin-lipid nanoparticles for fluorescence-guided photochemical tumour ablation and immune stimulation. PS can be radiolabelled with Copper-64 (<sup>64</sup>Cu-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 <sup>64</sup>Cu-PS and evaluated their pharmacology and toxicology in rats and dogs.</p> Methods <p><sup>64</sup>Cu-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 <sup>64</sup>Cu-PS dose was estimated in humans. </p> Results <p>Kit prepared <sup>64</sup>Cu-PS had high labelling yields and mean specific activities of 18.5&#xa0;MBq/mg (11.4&#xa0;GBq/mg max). The plasma PK of PS was linear between doses 0.5–15&#xa0;mg/kg in both rats and dogs. Tissue distribution was primarily to the liver. The estimated effective dose from <sup>64</sup>Cu-PS in humans was 38–47 µSv/MBq. Single doses of 32.6&#xa0;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&#xa0;mg/kg PS. Doses up to 15&#xa0;mg/kg PS were tolerated in dogs.</p> Conclusions <p>The pharmacology and safety profiles of PS and <sup>64</sup>Cu-PS in rats and dogs did not raise concerns regarding their use in humans. Radiolabelled <sup>64</sup>Cu-PS will permit accurate imaging-based assessments of nanoparticle PK and tumour uptake in imaging studies in cancer patients.</p>

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Radiopharmaceutical kit to prepare Copper-64 labelled porphyrin-lipid nanoparticles for radiotracer imaging studies in cancer patients

  • 期刊论文

  • 发表日期：

    2025年7月17日

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  • Michael S. Valic,
  • Carl J. Fisher,
  • Mark Zheng,
  • Alexander M. Gregor,
  • Wenlei Jiang,
  • Conrad Chan,
  • Harley H. L. Chan,
  • Abdullah El-Sayes,
  • Chris J. Zhang,
  • Tina Ye,
  • Michael Halim,
  • Pamela Schimmer,
  • Celina Li,
  • Nicholas Bernards,
  • Arthur C. K. Chu,
  • Zhongli Cai,
  • Juan Chen,
  • Jonathan C. Irish,
  • Kazuhiro Yasufuku,
  • Robert Weersink,
  • Raymond M. Reilly,
  • Brian C. Wilson,
  • Gang Zheng

摘要

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.