(PQD5) imaging systemic tissue injuries induced by anticancer drugs

Project: Research project

Description

Chemotherapeutic drugs are toxins for killing tumor cells, but their efficacy is often limited by the tolerance ceiling of normal tissues. A survey of systemic toxicity will provide valuable information on a new drug candidate for pharmaceutical development, and on the ther
apeutic regimen for existing drug combinations for each patient. The overall goal of this project is to develop and validate whole-body apoptosis imaging as a new approach for characterizing the systemic toxicity profile of anticancer drugs. Apoptosis is an important
manifestation of toxicity-induced tissue injuries. A whole-body scan, which we call “ToxScan”, detects tissue injuries systemically, in terms of a toxicity profile in response to the drug. We use a radiopharmaceutical, 99mTc-Duramycin, which detects exposed phosphatidylet
hanolamine in dead and dying cells. The imaging agent has binding affinity/specificity like an antibody yet clearance kinetics of a peptide. It is thus uniquely suited for whole-body imaging applications. Our central hypothesis is that a systemic toxicity profile reflects the
individual susceptibility to anticancer treatment. The scan provides indices for drug tolerance, and a prognostic indicator for chronic adverse effects. In preliminary studies, we demonstrated the sensitivity of whole-body 99mTc-Duramycin scan by detecting cell death in multiple tissues after a single clinically relevant dose of Doxorubicin. Whole-body apoptosis scan also revealed individualized response to the same therapeutic regimen. Single- and multi-organ indices for tissue injury are being derived for diagnostic and prognostic purposes. The evaluation of toxicity in such fashion will significantly accelerate the development of new anticancer drugs and new combination treatments. Ultimately, this approach will benefit oncology patients by optimizing therapies on a personalized basis.
StatusFinished
Effective start/end date5/7/144/30/19

Funding

  • National Cancer Institute (5R01CA185214-04)

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Whole Body Imaging
Wounds and Injuries
Pharmaceutical Preparations
Apoptosis
Antineoplastic Combined Chemotherapy Protocols
Drug Tolerance
Therapeutics
Antibody Specificity
Radiopharmaceuticals
Drug Combinations
Doxorubicin
Cell Death
Peptides
Neoplasms
technetium 99m HYNIC-duramycin