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.
Reference:
Mandiwana, V, Kalombo, L, Lemmer, Y, et al. Preclinical assessment of 68Ga‐PSMA‐617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging. Journal of Labelled Compounds and Radiopharmaceuticals, vol. 62(7): 332-345. https://doi.org/10.1002/jlcr.3747
Mandiwana, V., Kalombo, L., Lemmer, Y., Labuschagne, P. W., Semete-Makokotlela, B., Sathekge, M., ... Rijn Zeevaart, J. (2019). Preclinical assessment of 68Ga-PSMA-617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging. http://hdl.handle.net/10204/11063
Mandiwana, Vusani, Lonji Kalombo, Yolandy Lemmer, Philip W Labuschagne, Boitumelo Semete-Makokotlela, M Sathekge, T Ebenhan, and J Rijn Zeevaart "Preclinical assessment of 68Ga-PSMA-617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging." (2019) http://hdl.handle.net/10204/11063
Mandiwana V, Kalombo L, Lemmer Y, Labuschagne PW, Semete-Makokotlela B, Sathekge M, et al. Preclinical assessment of 68Ga-PSMA-617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging. 2019; http://hdl.handle.net/10204/11063.
Copyright: 2019 Wiley. Due to copyright restrictions, the attached PDF file only contains the abstract version of the full-text item. For access to the full-text item, please consult the publisher's website. The definitive version of the work is published in J Label Compd Radiopharm. 2019; 62: 332– 345. https://doi.org/10.1002/jlcr.3747