Using micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) for trace metal imaging in the development of MRI contrast agents for prostate cancer imaging

E Dao; M V Clavijo Jordan; K Geraki; A F Martins; S Chirayil; A D Sherry; M J Farquharson

doi:10.1016/j.jtemb.2022.127054

Using micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) for trace metal imaging in the development of MRI contrast agents for prostate cancer imaging

J Trace Elem Med Biol. 2022 Dec:74:127054. doi: 10.1016/j.jtemb.2022.127054. Epub 2022 Aug 3.

Authors

E Dao¹, M V Clavijo Jordan², K Geraki³, A F Martins⁴, S Chirayil⁵, A D Sherry⁶, M J Farquharson⁷

Affiliations

¹ Department of Physics & Astronomy, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, 72076, Germany. Electronic address: daoe@mcmaster.ca.
² Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, 72076, Germany.
³ Diamond Light Source, Harwell, Didcot OX11 0DE, United Kingdom; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, 72076, Germany.
⁴ Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen 72076, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, 72076, Germany.
⁵ Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, 72076, Germany.
⁶ Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, 72076, Germany; Department of Chemistry, University of Texas at Dallas, Richardson, TX 75080, United States.
⁷ Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, 72076, Germany; School of Interdisciplinary Science, McMaster University, Hamilton, ON L8S 4K1, Canada.

Abstract

Background: Contrast agents (CA) are administered in magnetic resonance imaging (MRI) clinical exams to measure tissue perfusion, enhance image contrast between adjacent tissues, or provide additional biochemical information in molecular MRI. The efficacy of a CA is determined by the tissue distribution of the agent and its concentration in the extracellular space of all tissues.

Methods: In this work, micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) was used to examine and characterize a gadolinium-based zinc-sensitive agent (GdL₂) currently under development for detection of prostate cancer (PCa) by MRI. Prostate tissue samples were collected from control mice and mice with known PCa after an MRI exam that included injection of GdL₂. The samples were raster scanned to investigate trends in Zn, Gd, Cu, Fe, S, P, and Ca.

Results: Significant Zn and Gd co-localization was observed in both healthy and malignant tissues. In addition, a marked decrease in Zn was found in the lateral lobe of the prostate obtained from mice with PCa.

Conclusion: We demonstrate here that µ-SRXRF is a useful tool for monitoring the distribution of several elements including Zn and Gd in animal models of cancer. The optimized procedures for tissue preparation, processing, data collection, and analysis are described.

Keywords: Contrast agent; Gadolinium; Prostate cancer; Synchrotron radiation; X-ray fluorescence; Zinc.

MeSH terms

Animals
Contrast Media
Fluorescence
Gadolinium / analysis
Humans
Magnetic Resonance Imaging
Male
Mice
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / pathology
Spectrometry, X-Ray Emission
Synchrotrons
Trace Elements* / analysis
X-Rays
Zinc / analysis

Substances

Contrast Media
Trace Elements
Gadolinium
Zinc

Grants and funding

R01 DK095416/DK/NIDDK NIH HHS/United States