@article{b28e91b2db204b2d9caf892bafaaa974,
title = "68Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography",
abstract = "Radiolabelled bisphosphonates (BPs) and [ 18F]NaF ( 18F-fluoride) are the two types of radiotracers available to image calcium mineral (e.g. bone), yet only [ 18F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using positron emission tomography (PET) imaging. These two radiotracers bind calcium mineral deposits via different mechanisms, with BPs chelating to calcium ions and thus being non-selective, and [ 18F]NaF being selective for hydroxyapatite (HAp) which is the main component of bone mineral. Considering that the composition of EC has been reported to include a diverse range of non-HAp calcium minerals, we hypothesised that BPs may be more sensitive for imaging EC due to their ability to bind to both HAp and non-HAp deposits. We report a comparison between the 68Ga-labelled BP tracer [ 68Ga]Ga-THP-Pam and [ 18F]NaF for PET imaging in a rat model of EC that develops macro- and microcalcifications in several organs. Macrocalcifications were identified using preclinical computed tomography (CT) and microcalcifications were identified using µCT-based 3D X-ray histology (XRH) on isolated organs ex vivo. The morphological and mineral analysis of individual calcified deposits was performed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). PET imaging and ex vivo analysis results demonstrated that while both radiotracers behave similarly for bone imaging, the BP-based radiotracer [ 68Ga]Ga-THP-Pam was able to detect EC more sensitively in several organs in which the mineral composition departs from that of HAp. Our results strongly suggest that BP-based PET radiotracers such as [ 68Ga]Ga-THP-Pam may have a particular advantage for the sensitive imaging and early detection of EC by being able to detect a wider array of relevant calcium minerals in vivo than [ 18F]NaF, and should be evaluated clinically for this purpose.",
author = "George Keeling and Fred Baark and Orestis Katsamenis and Jing Xue and Philip Blower and Sergio Bertazzo and {T. M. de Rosales}, Rafael",
note = "Funding Information: This work was funded by the EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1], Theragnostics Ltd., the Wellcome/EPSRC Centre for Medical Engineering [WT/203148/Z/16/Z], the MITHRAS EPSRC programme [EP/S032789/1] and the EPSRC [EP/H01506X/1]. Further support comes from a Wellcome Trust Multi User Equipment Grant [212885/Z/18/Z] and equipment Grant [WT 084052/Z/07/Z], the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and KCL [Grant Number IS-BRC-1215-20006] and the Biomedical Imaging Unit at the University of Southampton. This work was supported by the Wellcome Trust Biomedical Resource and Technology Development Grant 212940/Z/18/Z. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. This research was funded in whole, or in part, by the Wellcome Trust [WT 203148/Z/16/Z] [WT 212885/Z/18/Z] [WT 084052/Z/07/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Additionally, the authors would like to acknowledge the input of Professor Leon Schurgers, (Cardiovascular Research Institute Maastricht) and Dr Jayanta Bordoloi (The Francis Crick Institute). Funding Information: The authors declare the following competing financial interest(s): RTMR receives current funding from AstraZeneca plc (50% co-funding of a PhD studentship) for an unrelated project and has received past support from Theragnostics Ltd (50% co-funding of a PhD studentship for GK). RTMR receives consultant fees from ImaginAb Inc. All other authors declare no competing interests. Funding Information: This work was funded by the EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1], Theragnostics Ltd., the Wellcome/EPSRC Centre for Medical Engineering [WT/203148/Z/16/Z], the MITHRAS EPSRC programme [EP/S032789/1] and the EPSRC [EP/H01506X/1]. Further support comes from a Wellcome Trust Multi User Equipment Grant [212885/Z/18/Z] and equipment Grant [WT 084052/Z/07/Z], the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and KCL [Grant Number IS-BRC-1215-20006] and the Biomedical Imaging Unit at the University of Southampton. This work was supported by the Wellcome Trust Biomedical Resource and Technology Development Grant 212940/Z/18/Z. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. This research was funded in whole, or in part, by the Wellcome Trust [WT 203148/Z/16/Z] [WT 212885/Z/18/Z] [WT 084052/Z/07/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Additionally, the authors would like to acknowledge the input of Professor Leon Schurgers, (Cardiovascular Research Institute Maastricht) and Dr Jayanta Bordoloi (The Francis Crick Institute). Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",
year = "2023",
month = dec,
doi = "https://doi.org/10.1038/s41598-023-41149-7",
language = "English",
volume = "13",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}