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FP7

TARCC — Result In Brief

Project ID: 201962
Funded under: FP7-HEALTH
Country: France

Innovative anti-cancer radiopharmaceuticals

European researchers wished to address the challenge of cancer therapy by developing pharmaceuticals coupled to alpha-emitting radionuclides. The TARCC project's proposed approach envisioned site-specific tumour eradication without toxicity to healthy tissues.
Innovative anti-cancer radiopharmaceuticals
Scientists are searching for alternative therapies to increase the success of cancer treatment and to reduce detrimental side-effects. Being able to target only cancer cells and spare normal cells is a desirable property of any anti-cancer agent.

Based on this, the EU-funded 'Targeting alpha-particle emitting radionuclides to combat cancer' (TARCC) initiative proposed to develop targeted radionuclide therapy (TRT) for cancer. Partners will utilise alpha-emitting radionuclides (e.g. actinium-225, astatine-211 and bismuth-212) and develop new methods for radiolabelling biomolecules such as aminoacids (phenylalanine), peptides (somatostatin) or antibodies. The overall strategy of the TARCC study can be viewed at online.

The generated radiopharmaceuticals were directed to specific targets on the cancer cells and their binding affinities, cell uptake and retention were evaluated in vitro. To assess the therapeutic efficacy of their strategy in vivo, TARCC researchers used cancer mouse models and monitored tumour growth and overall animal survival. These studies were coupled with long-term toxicity monitoring.

Radiolabelled (bismuth-213) tumour-homing peptide F3 was effectively internalised into the nucleus of tumour cells and demonstrated therapeutic efficacy in a nude mouse model of peritoneal carcinomatosis. Another successful example of the TARCC strategy was the improved survival of a myeloma animal model treated with radiolabelled antibodies against the myeloma-expressing CD138 antigen. Similar efficacy in reducing tumour size and prolonging animal survival was seen in animal models of prostate, bladder and breast cancers.

Detailed dosimetry studies, estimation of the maximum tolerated activities and the radiobiological effects of selected radiopharmaceuticals revealed different cytotoxic effects compared to photons or electrons. Killing of tumour cells by alpha particles was independent of hypoxia. Alpha particles were also effective against cancer stem cells that are known to be resistant to chemotherapy and classical radiotherapy.

Collectively, the TARCC project results indicated that alpha-radionuclides are promising for targeted cancer therapy with minimal side-effects. This would considerably improve the quality of life of cancer sufferers’ and their families.

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