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Preclinical assessment of 68 Ga-PSMA-617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging.

Authors
  • Mandiwana, Vusani1, 2
  • Kalombo, Lonji1
  • Lemmer, Yolandy1
  • Labuschagne, Philip1
  • Semete-Makokotlela, Boitumelo1
  • Sathekge, Mike3
  • Ebenhan, Thomas3, 4
  • Zeevaart, Jan Rijn5, 2
  • 1 Centre for Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa. , (South Africa)
  • 2 DST/NWU, Preclinical Drug Development Platform, North West University, Potchefstroom, South Africa. , (South Africa)
  • 3 Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa. , (South Africa)
  • 4 Preclinical Imaging Facility, NuMeRI, Pelindaba, Pretoria, South Africa. , (South Africa)
  • 5 Radiochemistry, South African Nuclear Energy Corporation, Pelindaba, Pretoria, South Africa. , (South Africa)
Type
Published Article
Journal
Journal of Labelled Compounds
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jun 15, 2019
Volume
62
Issue
7
Pages
332–345
Identifiers
DOI: 10.1002/jlcr.3747
PMID: 31054157
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

It has in recent years been reported that microemulsion (ME) delivery systems provide an opportunity to improve the efficacy of a therapeutic agent whilst minimising side effects and also offer the advantage of favourable treatment regimens. The prostate-specific membrane antigen (PSMA) targeting agents PSMA-11 and PSMA-617, which accumulate in prostate tumours, allow for [68 Ga]Ga3+ -radiolabelling and positron emission tomography/computed tomography (PET) imaging of PSMA expression in vivo. We herein report the formulation of [68 Ga]Ga-PSMA-617 into a ME ≤40 nm including its evaluation for improved cellular toxicity and in vivo biodistribution. The [68 Ga]Ga-PSMA-617-ME was tested in vitro for its cytotoxicity to HEK293 and PC3 cells. [68 Ga]Ga-PSMA-617-ME was administered intravenously in BALB/c mice followed by microPET/computed tomography (CT) imaging and ex vivo biodistribution determination. [68 Ga]Ga-PSMA-617-ME indicated negligible cellular toxicity at different concentrations. A statistically higher tolerance towards the [68 Ga]Ga-PSMA-617-ME occurred at 0.125 mg/mL by HEK293 cells compared with PC3 cells. The biodistribution in wild-type BALB/C mice showed the highest amounts of radioactivity (%ID/g) presented in the kidneys (31%) followed by the small intestine (10%) and stomach (9%); the lowest uptake was seen in the brain (0.5%). The incorporation of [68 Ga]Ga-PSMA-617 into ME was successfully demonstrated and resulted in a stable nontoxic formulation as evaluated by in vitro and in vivo means. © 2019 John Wiley & Sons, Ltd.

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