(12) In addition to the promising results obtained by these studies, the procedure for the production of 211At-labeled antibodies under the current Good Manufacturing Practices (cGMP) toward clinical application was recently reported. (11−18) The 211At-labeled anti-Tenascin mAb 81C6 was administered locally to 18 patients with recurrent malignant brain tumors, (11) and the 211At-labeled MX35 F(ab′) 2, targeting the sodium-dependent phosphate transport protein 2B, was intraperitoneally administered to nine patients with ovarian cancer. (10) Furthermore, 211At-labeled antibodies were reportedly tested to deliver highly cytotoxic 211At to the target in preliminary investigations and preclinical situations. For delivering 211At to the desired regions, 211At-labeled small molecules, including uridine analogues, (6) benzylguanidine (a norepinephrine analogue), (7) biotin analogues, (8) a phenylalanine derivative, (9) and bisphosphonate complexes, have been previously designed. To harness the short path of α-particles and potent LET, 211At must be precisely delivered to the target. 207Bi results in stable 207Pb via its metastable states after the electron capture. The second branch (41.8%) directly decays through α-particle emission to 207Bi. (2−5) 211At is an α-emitter with a short half-life (7.2 h) and does not yield cytotoxic daughter isotopes during its decay the first branch (58.2%) decays through electron capture to 211Po (half-life: 516 ms), which decays through α-particle emission to 207Bi (half-life: 31.55 y). These properties render α-particles an attractive tool for treating intractable tumors. Owing to their high-energy emission within a short path length, α-particles can selectively eliminate target cells with minimal radiation damage to the surrounding normal tissues when delivered selectively to tumor tissues. (1) Compared with β-particles, α-particles have more potent linear energy transfer (LET) and a shorter path range. As for β-particles, two kinds of radiopharmaceuticals, which target the CD20 molecule on the surface of lymphoma cells, 90Y-labeled rituximab and 131I-labeled rituximab, have already shown clinical benefits against CD20-positive non-Hodgkin B-cell lymphoma. RIT has expanded the applications of radiotherapy from focusing on local tumors to targeting scattered tumors, such as distant metastases and disseminated lesions. Radioimmunotherapy (RIT) is defined as targeted radionuclide therapy using radiolabeled antibodies.
0 Comments
Leave a Reply. |