IART® stands for Intraoperative Avidination for Radionuclide Treatment. It is a multicomponent product based on technology involving a sequence of injections of substances that interact with each other. The substance Avidin is injected intra-operatively by the surgeon into the operated tumor bed. Biotinylated human serum albumin is then administered post-operatively to wipe out the excess of circulating avidin. Finally, either 111In-labeled (for Imaging) or 90Y-labeled biotin (90Y-DOTA-biotin) (for treatment) is administered post-operatively to the patient. Very recently 177Lu replaced 90Y and the development of the drug was resumed under the name 177Lu-ST2210.
The avidin–biotin bond is one of the strongest bonds existing in nature and allows concentration of Radioactivity at the site where avidin was injected and only there.
In the 1990s, this technology had already been used in glioblastoma. The most recent trials targeted breast cancer. However, this technology, which is actually a nice way to concentrate Radioactivity in a specific delimited area, can be used in any well-identified solid tumor. There is in principle no limitation for its application as no biological interaction with the tumor cells is involved. A new potential is open in prostate cancer and should be explored as well.
Phase I and II clinical trials have been performed in breast cancer patients. A Phase II trial in 35 patients demonstrated that the radioactive drug provides a boost of 20 Gy concentrated in the tumor alone. This positive result should be sufficient to start a Phase III trial. A new phase I trial has been initiated in 2014, in patients with liver metastases from colon cancer. In June 2017, a new study was initiated using 177Lu-DOTA-Biotin instead of the 90Y-labeled drug. At this stage, unfortunately, this drug continues to be developed only at the academic level as it is difficult to link IP on it.
Target/Mechanism: Avidin
Leading Emitter: beta electrons (β–)