Insights into Trace Metal Metabolism in Health and Disease from PET: “PET Metallomics”

Abstract

This review highlights opportunities that now present themselves, exemplified by studies of copper metabolism that are in the vanguard of a new research front in molecular imaging: "PET metallomics."

In vivo [64Cu]CuCl2 PET imaging reveals activity of Dextran-Catechin on tumor copper homeostasis

“…PET with intravenous [ 64 Cu]CuCl 2 was previously evaluated in several preclinical cancer models as a potential diagnostic tool 24 . Although some studies found no correlation of intravenous [ 64 Cu]CuCl 2 uptake with CTR1 expression in cancer cells 25 , there are other works which suggest a key role of CTR1 in copper uptake and its intracellular homeostasis 26 .…”

“…These observations suggest that CTR1 expression is important in regulating the tumor uptake of copper, but it is not the sole player. In fact, it is well known that copper levels depend also on the subcellular localization of CTR1 which can differ between tumor types, and that copper homeostasis is also regulated by copper efflux transporters ATP7A and ATP7B 24 . All these factors can influence intracellular copper levels, and this may be the reason for conflicting evidence reported on the utility of [ 64 Cu]CuCl 2 for tumor diagnosis.…”

New highlight in breast cancer development: the key role of hepcidin and iron metabolism

“…In fact, currently, numerous radiotracers as 52 Fe-citrate are able to track iron particles in peculiar human pathologies such as Wilson's disease (17). Moreover, there is an increase of iron in the brain with aging and increased iron levels were observed along with deposits of senile plaque in Alzheimer patients (18). Similarly, this approach could be proposed for the screening of breast cancer patients in order to identify the lesions with high probability to develop bone lesions.…”

Across the spectrum: integrating multidimensional metal analytics forin situmetallomic imaging

“…3B). 79 PET metallomics is certainly in its infancy, but already promising 64 Cu PET studies are appearing in the literature within the context of Wilson's disease, dementia and cancer, with the potential to improve diagnostics and complement or even replace biopsies 80–84…”