Impact of Dietary Zinc on Stimulated Zinc Secretion MRI in the Healthy and Malignant Mouse Prostate

Academic Background

Zinc (Zn²⁺) is an essential trace element in biological systems, participating in various physiological processes, including enzyme catalysis, structural regulation of transcription factors, immune system modulation, and cell proliferation, differentiation, and survival. The prostate is one of the tissues with the highest zinc content in the human body, and zinc levels are significantly reduced in patients with prostate cancer (PCA). This phenomenon has drawn researchers’ attention to the role of zinc in prostate health and disease. In recent years, the development of the zinc-responsive MRI probe, GdL1, has made it possible to detect zinc secretion through MRI imaging, particularly in studies of glucose-stimulated zinc secretion (GSZS). GdL1 can distinguish between healthy and malignant prostate tissues.

However, dietary zinc intake varies widely and may affect zinc content and secretion in prostate tissues. Therefore, this study aims to investigate the impact of different dietary zinc intakes on zinc content and secretion in the prostate tissues of healthy and malignant mice, providing new insights for MRI detection of prostate cancer.

Source of the Paper

This paper was co-authored by Veronica Clavijo Jordan, André F. Martins, Erica Dao, and others, from multiple research institutions, including Harvard Medical School, the University of Tübingen, McMaster University, and the University of Texas Southwestern Medical Center. The paper was published in npj Imaging in 2024.

Research Process and Results

Study Design

This study employed molecular magnetic resonance imaging (MRI) and synchrotron radiation X-ray fluorescence (SR-XRF) techniques to explore the impact of dietary zinc intake on zinc content and secretion in the prostate tissues of healthy and malignant mice. The experiment was divided into three dietary groups: low-zinc (0.05 ppm), normal-zinc (30 ppm), and high-zinc (150 ppm) diets, fed for 21 days before imaging analysis.

Experimental Steps

1. Animal Models and Dietary Control: Wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed low-zinc, normal-zinc, and high-zinc diets for 21 days.
2. MRI Imaging: Before imaging, mice were fasted overnight and injected with the GdL1 probe via the tail vein and glucose intraperitoneally to stimulate zinc secretion. T1-weighted imaging was performed using a 9.4 T MRI scanner to record prostate images before and after injection.
3. SR-XRF Analysis: After imaging, mice were euthanized, and prostate tissues were rapidly frozen and sectioned for SR-XRF analysis to detect zinc distribution in the tissues.
4. Blood Analysis: Blood samples were collected, and serum zinc levels were measured using inductively coupled plasma mass spectrometry (ICP-MS).

Key Results

1. Impact of Dietary Zinc on Body Weight and Zinc Bioavailability: Low-zinc diets led to significant weight loss in mice, and healthy mice showed increased serum zinc levels under low-zinc diets, while TRAMP mice failed to effectively regulate serum zinc levels.
2. Zinc Distribution in Prostate Tissues: SR-XRF analysis revealed that zinc content in the prostate tissues of healthy mice did not differ significantly among dietary groups, while zinc content in TRAMP mice was significantly reduced.
3. MRI Detection of GSZS: MRI imaging showed that zinc secretion in healthy mice significantly increased under glucose stimulation, and the secretion was proportional to dietary zinc intake. In contrast, TRAMP mice exhibited significantly reduced zinc secretion, which was unaffected by dietary zinc intake.

Conclusion

This study demonstrates that dietary zinc intake significantly affects zinc secretion in the prostate tissues of healthy mice, while TRAMP mice, due to reduced zinc storage capacity in malignant cells, exhibit significantly lower zinc secretion. This finding suggests that dietary zinc supplementation prior to GSZS MRI may enhance image contrast between healthy and malignant prostate tissues, thereby improving the accuracy of prostate cancer detection.

Research Highlights

1. MRI Detection of Zinc Secretion: For the first time, MRI imaging was used to detect the impact of dietary zinc intake on prostate zinc secretion, providing a new method for non-invasive detection of prostate cancer.
2. Impact of Dietary Zinc: The study revealed differences in zinc content and secretion in healthy versus malignant prostate tissues due to dietary zinc intake, offering a theoretical basis for early diagnosis of prostate cancer.
3. Validation of the TRAMP Model: The TRAMP mouse model validated the reduced zinc storage and secretion capacity in malignant prostate tissues, further supporting the critical role of zinc in prostate cancer.

Research Significance

This study not only deepens the understanding of zinc’s role in prostate health and disease but also provides new insights for MRI detection of prostate cancer. By regulating dietary zinc intake, the accuracy of GSZS MRI detection may be improved, offering potential applications for early diagnosis and treatment of prostate cancer.

Additional Valuable Information

The GdL1 probe used in this study has been patented multiple times and licensed to VitalQuan for commercial development. Additionally, the study uncovered the potential role of zinc in glucose metabolism, providing new directions for future research on zinc’s function in metabolic diseases.

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Through this research, we have not only enhanced our understanding of zinc’s role in prostate health and disease but also provided new technological tools for the non-invasive detection of prostate cancer. In the future, with further optimization and clinical application of the GdL1 probe, GSZS MRI detection is expected to become an important tool in prostate cancer diagnosis.