Litchfield, Marcus, Wuest, Melinda, Glubrecht, Daryl, Briard, Emmanuelle, Auberson, Yves, McMullen, Todd, Brindley, David and Wuest, Frank (2021) PET Imaging of Autotaxin in Thyroid and Breast Cancer Models using [18F]PRIMATX. Molecular pharmaceutics.

Abstract

Autotaxin (ATX) is a secreted enzyme responsible for producing lysophosphatidic acid (LPA). The ATX/LPA signalling axis is typically activated in wound healing and tissue repair processes. It is highjacked and upregulated in the progression and persistence of several chronic inflammatory diseases, including cancer. As ATX inhibitors are now progressing to clinical testing, innovative diagnostic tools such as positron emission tomography (PET) are needed for the exact and accurate measurement of ATX expression in vivo. Recently, a radiotracer, [18F]PRIMATX, was developed and tested for PET imaging of ATX in vivo in a murine melanoma model. The goal of the present work was to further validate [18F]PRIMATX as a PET imaging agent by analyzing its in vivo metabolic stability and suitability for PET imaging of ATX in models of human 8305C thyroid tumour and murine 4T1 breast cancer. [18F]PRIMATX displayed favourable metabolic stability in vivo (65% of intact radiotracer after 60 min p.i.) and provided sufficient tumour uptake profiles in both tumour models. Radiotracer uptake could be blocked by 8-12% in 8305C thyroid tumours in the presence of ATX inhibitor AE-32-NZ70 as determined with PET and ex vivo biodistribution analyses. [18F]PRIMATX also showed high brain uptake, which was reduced by 50% through the administration of ATX inhibitor AE-32-NZ70. [18F]PRIMATX is a suitable radiotracer for PET imaging of ATX in the brain and peripheral tumour tissues.

Item Type:	Article
Keywords:	Fluorine-18, positron emission tomography (PET), autotaxin (ATX), lysophosphatidic acid (LPA), molecular imaging
Date Deposited:	27 Aug 2021 00:45
Last Modified:	27 Aug 2021 00:45
URI:	https://oak.novartis.com/id/eprint/44608