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Novel imaging agent identifies biomarker for iron-targeted cancer therapies

Novel imaging agent identifies biomarker for iron-targeted cancer therapies
2021-07-23
(Press-News.org) Reston, VA--A new radiotracer that detects iron in cancer cells has proven effective, opening the door for the advancement of iron-targeted therapies for cancer patients. The radiotracer, 18F-TRX, can be used to measure iron concentration in tumors, which can help predict whether a not the cancer will respond to treatment. This research was published in the July issue of the Journal of Nuclear Medicine.

All cancer cells have an insatiable appetite for iron, which provides them the energy they need to multiply. As a result, tumors have higher levels of iron than normal tissues. Recent advances in chemistry have led scientists to take advantage of this altered state, targeting the expanded cytosolic 'labile' iron pool (LIP) of the cancer cell to develop new treatments.

A clear method to measure LIP in tumors must be established to advance clinical trials for LIP-targeted therapies. "LIP levels in patient tumors have never been quantified," noted Adam R. Renslo, PhD, professor in the department of pharmaceutical chemistry at the University of California, San Francisco. "Iron rapidly oxidizes once its cellular environment is disrupted, so it can't be quantified reliably from tumor biopsies. A biomarker for LIP could help determine which tumors have the highest LIP levels and might be especially vulnerable to LIP-targeted therapies."

To explore a solution for this unmet need, researchers imaged 10 tissue graft models of glioma and renal cell carcinoma with 18F-TRX PET to measure LIP. Tumor avidity and sensitivity to the radiotracer were assessed. An animal model study was also conducted to determine effective human dosimetry.

18F-TRX showed a wide range of tumor accumulation, successfully distinguishing LIP levels among tumors and determining those that might be most likely to respond to LIP-targeted therapies. Pretreatment 18F-TRX uptake in tumors was also found to predict sensitivity to therapy. The estimated effective dose for adults was comparable to those of other 18F-based imaging agents.

"Iron dysregulation occurs in many human disorders, including neurodegenerative and cardiovascular diseases, and inflammation," said Michael J. Evans, associate professor in residence in the department of radiology and biomedical imaging at the University of California, San Francisco. "Applying 18F-TRX in the respective patient populations to define the extent of LIP expansion in affected tissues will be an important milestone toward understanding the therapeutic potential of LIP-targeted therapies beyond oncology."

INFORMATION:

This study was made available online in November 2020 ahead of final publication in print in July 2021.

The authors of "Ferronostics: Measuring Tumoral Ferrous Iron with PET to Predict Sensitivity to Iron-Targeted Cancer Therapies" include Ning Zhao, Yangjie Huang, Yung-hua Wang, Ying-Chu Chen, Nima Hooshdaran, Junnian Wei, Pavithra Viswanath, Youngho Seo, Davide Ruggero, Adam R. Renslo and Michael John Evans, University of California, San Francisco, San Francisco, California; and Ryan K. Muir, Stanford University, Stanford, California.

Funding: This study was supported by an American Cancer Society research scholar grant (130635-RSG-17-005-01-CCE), the CDMRP Prostate Cancer Program (W81XWH-18-1-0763, W81XWH-16-1- 0435, and W81XWH1810754), and the National Institutes of Health (R01AI105106). Ryan Muir, Adam Renslo, and Michael Evans are listed as inventors on patent applications describing 18F-TRX and related radiotracers. Adam Renslo is a cofounder of and advisor to Tatara Therapeutics, Inc. No other potential conflict of interest relevant to this article was reported.

Visit JNM's new website for the latest research, and follow our new Twitter and Facebook pages @JournalofNucMed.

Please visit the SNMMI Media Center for more information about molecular imaging and precision imaging. To schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or rmaxey@snmmi.org

About JNM and the Society of Nuclear Medicine and Molecular Imaging

The Journal of Nuclear Medicine (JNM) is the world's leading nuclear medicine, molecular imaging and theranostics journal, accessed more than 11 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field. Current and past issues of the Journal of Nuclear Medicine can be found online at http://jnm.snmjournals.org.

JNM is published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging--precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes. For more information, visit http://www.snmmi.org.


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Novel imaging agent identifies biomarker for iron-targeted cancer therapies

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[Press-News.org] Novel imaging agent identifies biomarker for iron-targeted cancer therapies