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January 9, 2021 // -- A cancer-specific L-type amino acid transporter protein (LAT1) is often highly expressed in cancer tissue, inhibiting the function of LAT1 or producing anti-tumor effects, but researchers are currently making very limited progress in developing radionuclide therapy (radionuclide therapy) that targets LAT1.
, scientists from Osaka University in Japan and others developed a targeted α therapy to target LAT1, using a new drug, according to a recent study published in the international journal Cansr Science.
article, researchers first developed the α-ray transmitter 211 (At, Astatine), which may not be easy for scientists given that At is the rarest element of natural existence on Earth.
-targeted α therapy is able to selectively transport α-ray emitters to tumor tissue, and the advantage over traditional β therapies is that the attenuation of α-rays is highly targeted, and the transfer of high linear energy causes DNA double strands to break, effectively inducing cell death.
α radiation has a shorter half-life and limited tissue penetration, it ensures a higher therapeutic effect and fewer side effects on surrounding normal cells.
Photo Source: Osaka University Next, in order to carry radioisotopes into cancer cells, researchers attached them to α-methyl-L tyrosine α, which has a high affinity for LAT1, a design that exploits the increased nutritional needs of rapidly increasing value-added cancer cells.
researcher Professor Kazuko Kaneda-Nakashima said: 'We found that 211At-labeled α-methyl-L tyrosine (211At-AAMT) has a high affinity for LAT1, which effectively inhibits tumor cells and promotes DNA double-stranded fragmentation in-body.
Then the researchers expanded their study further, evaluating the accumulation of 211At-AAMT and the role of LAT1 in the experimental mouse model, and after further study of the human pancreatic cancer cell line, the researchers found that 211At-AAMT selectively accumulated and inhibited its growth in tumors and, at higher doses, even inhibited the metastasis of cancer in the lungs in metastatic melanoma mouse models. 'Now we can determine the effectiveness of 211At in treating cancers, including advanced and metastases, and also use amino acid transport protein LAT1 as a transporter of radionuclide therapy, which can be absorbed by cancer cells as nutrients to attack cancer within cells when it is transported to cancer,' said atsushi Shinohara, a
researcher.
This new treatment increases efficacy and is easy to administration, and as an injectable short-range radioactive drug, 211At can also be used in outpatient clinics, which has a greater advantage than traditional radiotherapy and can even be used as an alternative to specific cancer surgery.
The new approach has great potential to revolutionis radionuclide therapy, not only by effectively treating pancreatic cancer, but also by helping to treat malignant tumors that lack effective treatment, including advanced or metastatic cancer.
original source: Kazuko Kaneda-Nakashima et al. α-Emitting cancer therapy using 211 At-AAMT targeting LAT1, Cancer Science (2020). DOI:10.1111/cas.14761