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Evaluation of cyclotron produced radiometals for radiolabeling of immuno- and bio-conjugates for nuclear imaging.

University of British Columbia

The development of novel bioconjugates; antibodies, antibody mimetics and peptides is revolutionising the targeted molecular imaging approach to oncology. Many bioconjugates with high and specific uptake in tumours are transitioning into clinical oncology imaging. Monoclonal antibodies are returning to diagnostic imaging due to the clinical impact and commercial success of many disease-modifying monoclonal antibodies and antibody-drug conjugates. One hindrance to mAb based imaging is their long biological half-life; requiring days to visualise high tumour-to-non-target contrast. A variety of avenues to improve the contrast and clearance of circulating mAbs are in development. Radiometals that are well suited for imaging antibodies as well as antibody mimentics or peptides are becoming more in demand as clinical translation occurs. Current constraints and requirements for conventional radiometal production can limit the accessibility to certain cyclotron centers and may not be easily integrated into existing cyclotron centers. Efforts have been made to modify conventional radiometal production by introducing a liquid target approach. Limitations with yield and purification methods are hindering the feasibility of producing radiometals with a liquid target. Herein, we propose to produce radiometals with a liquid target and compare yields, optimize purification procedures to ensure high radiolabeling yields and assess their usefulness to radiolabel existing and novel bioconjugates. Additionally, we use a variety of strategies to improve tumour-to-non-target contrast ratios and pharmacokinetics of mAbs which can be applied to imaging of novel mAbs. We demonstrate the ability to produce and purify ⁸⁹Zr with both a solid and liquid target with sufficient yields for radiolabeling of antibodies. We demonstrate that liquid target produced ⁸⁹Zr is a suitable alternative approach to conventional solid target ⁸⁹Zr by demonstrating suitable antibody radiolabeling yields for in vivo imaging. We demonstrate that liquid target produced ⁶⁸Ga can be separated effectively from the staring zinc material and from other metal impurities. This successful purification enabled high radiolabeling of DOTATOC. The radiolabeled ⁶⁸GaDOTATOC from liquid target ⁶⁸Ga was compared with an in vivo study to that of conventional generator ⁶⁸Ga. We demonstrate the feasibility of producing, purifying and radiolabeling liquid target ⁶⁸Ga for in vivo imaging.

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2018-08-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/62734

Interdisciplinary Oncology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/