Kinetics of Nanoparticle Radiolabeling of Metalloporphyrin with 64Cu for Positron Emission Tomography (PET) Imaging

Leon Z. Wang, Tristan L. Lim, Prashanth K. Padakanti, Sean D. Carlin, Abass Alavi, Robert H. Mach, Robert K. Prud'Homme

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Porphyrins are a unique class of biocompatible molecules with strong light absorption and rich coordination chemistry, leading to their use as chelating agents in applications such as biomedical imaging. In particular, clusters of chelators inside a nanoparticle core can be used as contrast agents for positron emission tomography. However, the mechanism of metal chelation by porphyrins encapsulated in the hydrophobic core of a nanoparticle, an essential step in radiolabeling, has not been addressed. Here, we present a study on the kinetics of copper chelation into hematoporphyrin derivative (HpD)-encapsulated nanoparticles. Nanoparticles of 100 nm, containing HpD and sterically stabilized by a poly(ethylene glycol) block copolymer, were prepared by the kinetically controlled, rapid precipitation process Flash NanoPrecipitation. When incubated with copper ions, these HpD nanoparticles exhibit novel chelation behavior. The experimental data on UV-vis absorption and reaction modeling of the two-step chelation reaction support the formation of an intermediate complex. The reaction rates of the initial binding and the final chelation step are kon = 0.231 h-1 μM-1 and kst = 1.095 h-1, respectively. The initial binding occurs within the first 20 min and converts to the firmly chelated, metalloporphyrin. Understanding the kinetics of the binding enables the next step in advancing this technology to medical diagnostics.

Original languageEnglish (US)
Pages (from-to)19126-19132
Number of pages7
JournalIndustrial and Engineering Chemistry Research
Volume59
Issue number43
DOIs
StatePublished - Oct 28 2020

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)
  • Industrial and Manufacturing Engineering

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