Breast, prostate, and pancreatic cancers alter the zinc (Zn) metabolism. Combined analyses of urinary Zn concentrations [Zn] and Zn stable isotope compositions (δ⁶⁶Zn) may provide a non-invasive approach for tracing malignancy-induced Zn dyshomeostasis. In this study, we measured [Zn] and δ⁶⁶Zn in urine from prostate (n = 22), breast (n = 16), and from women with benign breast disease (n = 14) and compared those with age-matched healthy controls (22–49 years or 50+ years) and published data for pancreatic cancer (n = 17). Our results show that cancer-induced changes are reflected in higher urinary [Zn] and lower urinary δ⁶⁶Zn for pancreatic and prostate cancer and benign breast disease when compared with healthy controls. For prostate cancer, the progression of low [Zn] and high δ⁶⁶Zn for patients of low-risk disease toward high [Zn] and low δ⁶⁶Zn for the higher risk patients demonstrates that [Zn] and δ⁶⁶Zn in urine could serve as a reliable prognostic tool. Urinary excretion of isotopically light Zn by patients with prostatic and pancreatic cancer is probably the result of increased reactive oxygen species in cancerous cells, which limits the scavenging of hydroxyl radicals and thus facilitates the oxidation of metalloproteins with sulfur-rich ligands. Urine from breast cancer patients shows undistinguishable δ⁶⁶Zn to healthy controls, implying that the expression of metalloproteins with sulfur-rich ligands is stronger in breast cancer tissues. In conclusion, urinary δ⁶⁶Zn may provide a non-invasive diagnostic tool for pancreatic cancer and support disease prognosis for prostate cancer. These findings should translate to comprehensive transverse and longitudinal cohort studies in future.

Measurements of Cu isotopes from low concentration and high salinity matrices require high recovery and purity, prior to measurement. An automated two-stage chromatographic procedure, combining a pre-purification stage to remove the majority of matrix elements (AG® 50W-X12), with an adaptation of an existing method using anion exchange resin AG®MP-1 has been used to overcome these problems. A series of matrices were tested, from low (river water) to high salinity (synthetic seawater, human serum), using several standards and reference materials such as Trace Metals 1 (−0.21‰ ± 0.08 2SD), SLRS-5 (+0.30‰ ± 0.05 2SD), Seronorm™ (−0.25‰ ± 0.04 2SD), and NASS-7 seawater, doped with ERM®-AE633 (0.00‰ ± 0.14 2SD). Results demonstrated highly pure (>98%) Cu separations, low procedure blanks (<1% of loaded Cu), and much improved measurement reproducibility of <0.14‰ (2SD) for high salinity samples. This is an important development for δ⁶⁵Cu measurement from low Cu concentrations commonly encounted in research of medical isotope metallomics, mineral exploration, and environmental geochemistry. As with other studies, combining standard-sample bracketing with Ga for internal normalisation to correct instrumental mass bias (C-SSBIN) resulted in a significant improvement in the precision of measurements (versus standard sample bracketing alone), typically improving the external reproducibility of measurements from 0.10 down to 0.03‰ (2SD).

The disruption of Zn homeostasis has been linked with breast cancer development and progression. To enhance our understanding of changes in Zn homeostasis both inside and around the tumour microenvironment, Zn concentrations and isotopic compositions (δ⁶⁶Zn) were determined in benign (BT) and malignant (MT) tumours, healthy tissue from reduction mammoplasty (HT), and histologically normal tissue adjacent to benign (NAT(BT)) and malignant tumours (NAT(MT)). Mean Zn concentrations in NAT(BT) are 5.5 µg g⁻¹ greater than in NAT(MT) (p = 0.00056) and 5.1 µg g⁻¹ greater than in HT (p = 0.0026). Zinc concentrations in MT are 12.9 µg g⁻¹ greater than in HT (p = 0.00012) and 13.3 µg g⁻¹ greater than in NAT(MT) (p < 0.0001), whereas δ⁶⁶Zn is 0.17‰ lower in MT than HT (p = 0.017). Benign tumour Zn concentrations are also elevated compared to HT (p = 0.00013), but are not significantly elevated compared to NAT(BT) (p = 0.32). The δ⁶⁶Zn of BT is 0.15‰ lower than in NAT(BT) (p = 0.045). The similar light δ⁶⁶Zn of BT and MT compared to HT and NAT may be related to the isotopic compensation of increased metallothionein (⁶⁴Zn-rich) expression by activated matrix metalloproteinase (⁶⁶Zn-rich) in MT, and indicates a resultant ⁶⁶Zn-rich reservoir may exist in patients with breast tumours. Zinc isotopic compositions thus show promise as a potential diagnostic tool for the detection of breast tumours. The revealed differences of Zn accumulation in healthy and tumour-adjacent tissues require additional investigation.

In the last 20 years, the application of high-precision isotopic analysis of essential mineral elements (Mg, K, Ca, Fe, Cu and Zn) to biomedicine (sometimes referred to as isotope metallomics), has revealed that their stable isotopic compositions are altered by the metal dysregulation that is fundamental to the pathogenesis of many cancers and other diseases. Despite many published works showing the diagnostic and prognostic potential of this approach, a number of factors that may influence the stable isotopic composition of these essential mineral elements in healthy individuals remain unstudied. In this perspective article, we summarize the available evidence from studies of archaeology, anthropology, ecology, animal models, and living humans relating to physiological and lifestyle factors that appear likely (there is evidence indicating their influence) or unlikely (there is evidence indicating their lack of influence) to require controlling for when investigating variations in essential mineral element isotopic compositions in human subjects. We also discuss factors that require additional data to properly assess. There is evidence that sex, menopausal status, age, diet, vitamin and metal supplementation, genetic variation, and obesity influence the isotopic composition of at least one essential metal in the human body. The task of investigating potential influences on essential mineral element isotopic compositions in the human body is sizeable, but presents an exciting research opportunity, with each incremental advance helping to improve the quality of research output in the context of isotope metallomics.