TGW211 for Click-Cleavable Imaging in HER2-Positive Cancers.

In recent years, there is increasing interest in antibodies for imaging, antibody-drug conjugates (ADC) and targeted radionuclide therapy (TRT). With these techniques, antibodies are used as a vector to deliver a cytotoxic drug or radionuclide for therapy or nuclear medicine imaging. One such antibody-based vector suitable for delivering a cytotoxic drug or radionuclide is trastuzumab, which targets HER2 that is overexpressed in cancers such as breast, gastric and gastroesophageal junction carcinomas. Unfortunately, antibodies generally have a very long circulation time (\>20-30 days) that often result in unfavorable background noise in the healthy organs in imaging or toxicity when trastuzumab is bound to a therapeutic radionuclide for radioimmunotherapy. There is thus a need to increase the speed of excretion of antibodies or release the antibody from its payload. Ideally, the clinician would like to appropriately time the elimination of radioactivity to achieve an optimal tumor to non-tumor ratio. To this aim, Tagworks Pharmaceuticals developed a new class of chemically cleavable radiolabeled conjugates that release the radiolabel on demand upon reaction with a small molecule "the trigger" (TRG001).

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