Project title: Tumor-specific delivery of temozolomide to overcome resistance in GEP-NETs

Ali Azhdarinia, PhD, University of Texas, will explore the efficacy of Ga-68 dotatoc in treating NETs in the gastrointestinal tract and pancreas.

What questions will researchers try to answer?

A major problem with traditional chemotherapeutics is that they induce systemic toxicity, which means that while they may kill tumor cells, they may also kill healthy cells. These “off-target” or “side” effects of some drugs severely limit their use and effectiveness for tumor-killing potential. Azhdarinia will try to direct the drugs specifically to the tumors in the body to increase their effectiveness and decrease their off-target effects.

Why is this important?

Azhdarinia will test whether image-guided drug delivery (IGDD) can enhance chemotherapy delivery to the tumors, using imaging to visualize the drug in the body to monitor drug uptake by tumors. Up to now, researchers have not yet demonstrated the effectiveness or safety of this therapeutic strategy.

What will researchers do?

Azhdarinia will test whether the PET imaging agent, Ga -68 dotatoc can be effectively coupled with a chemotherapy drug (TMZ) in a way that could be reliably used to treat NETs. He will start with preclinical experiments in laboratory animals. The imaging agent used to “light up” neuroendocrine tumors in scans will be chemically linked with TMZ, a drug already shown to have clinical efficacy. Ga-68 dotatoc binds to the somatostatin receptors that are specifically concentrated on neuroendocrine tumor cells, thus targeting the drug specifically to the cancer cells, but not to normal cells.

How might this improve the treatment of NETs?

By targeting chemotherapy to NET cells via their somatostatin receptors, IGDD could result in delivering higher, more effective drug doses to the cancer cells and reducing damage to healthy cells. It is also conceivable that targeting chemotherapeutics to the tumor cells may also contribute to averting drug resistance.

What is the next step?

As a preliminary investigation of IGDD, this study explores the ability to pair a chemotherapy drug with an imaging agent to test therapeutic efficacy in the laboratory. If the IGDD concept shows promise, it would then undergo further testing to understand whether the approach can be translated to work in human patients.

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