Pancreatic neuroendocrine tumors (NETs), are rare morphologically well-differentiated malignancies with an unacceptably poor 5-year survival rate of 20%. Multiple lines of evidence suggest that immunosuppressive Tregs play a critical role in preventi

Year: 2016
Institution: University College London
Country: United Kingdom
Award Type: NETRF GRANTS 2005-2017
NET Type: Pancreas
Science Type: Translational

Description

Schaffer and his team will study a new chelate, or compound, that holds the radionuclinde called Ac-225. They are testing whether Ac-225-crown-TATE compound can safely and effectively treat tumors and prolong the survival of tumor-bearing models.

What question will the researchers try to answer?

Targeted radionuclide therapy involves developing tumor-specific drugs that can carry particle-emitting radioactive isotopes to tumors. The accumulation of these radiopharmaceuticals that contain toxic radionuclides will cause targeted cell death while sparing surrounding healthy tissue. Actinium-225 (Ac-225) is an alpha-emitting isotope that is showing significant clinical response in some advanced, untreatable cancers. A major hurdle in developing Ac-radiopharmaceuticals includes finding ways of attaching Ac-225 to drug carrier molecules. Dr. Schaffer’s research aims to demonstrate that a novel actinium chelate, or compound, can incorporate the radioisotope into molecules targeted toward the somatostatin receptor – an important cellular marker in some neuroendocrine tumors.

Why is this important?

Actinium is unstable, so drugs made with this isotope cannot be stockpiled. Dr. Schaffer and his team will demonstrate a chelate designed to incorporate the isotope under mild conditions, allowing pharmacists to easily produce and administer the radiopharmaceutical in a hospital setting. This project will also demonstrate the efficacy of the radiopharmaceutical for treating somatostatin-positive tumors.

What will researchers do?

Dr. Schaffer’s team will establish the radiopharmaceutical synthesis protocol and perform biodistribution studies to establish the toxicity and therapeutic response of somatostatin-positive neuroendocrine tumors. 

How might this improve the treatment of NETs?

Synthesizing actinium-labeled radiopharmaceuticals will enable the treatment of advanced, metastatic disease for which no other treatment options exist. 

What is the next step?

They will begin by synthesizing the drug precursors and label them with actinium produced at TRIUMF in Vancouver, Canada. Tumor-bearing models will receive escalating doses of the radiopharmaceutical to establish dose tolerance and tumor response.