It is therefore worthwhile to present several cases of successful TRNT of solid tumors. For example, the clinical practice of targeted radionuclide therapy of metastases of hepatic colorectal carcinoma involved the use of anti-CEA antibodies, which were employed to produce a conjugate with 131I isotopes. The median survival time in such TRNT was approximately 68 months, with the median of complete remission duration of 18 months [55]. The treatment of castration-resistant prostate cancer, where antibodies against PSMA antigen were utilized to produce a conjugate with 177Lu radionuclides represent another successful approach, achieving the median survival time up to 10 months [56]. In stage IV melanoma treatment antibodies against NG2 were used with a radionuclide 213Bi. In 50% of patients, a long-lasting stable course of the disease was registered, while 14% had a partial remission [57]. Metastasizing melanoma therapy included anti-NG2 antibodies with radionuclide 213Bi, and the median survival time in that targeted radionuclide therapy was increased by nine months [58].
RPT has had the greatest historical impact for thyroid malignancies and this persists to the present day. Haematological malignancies were investigated starting in the early 1990s and continue to be a subject of interest. RPT for hepatic malignancies and prostate cancer has seen the greatest increase since the 1980s. This increase is consistent with the development of new RPT agents, 90Y-loaded microspheres and β-emitter-labelled and α-emitter-labelled small-molecule prostate-specific membrane antigen (PSMA)-targeting constructs, respectively (see later). The FDA-approved α-emitter 223Ra has also driven the substantial increase in interest in RPT for prostate cancer. Other solid cancers such as colorectal and breast cancer continue to be of interest but have not had the breakthrough construct development that has driven interest in RPT in hepatic and prostate cancer. Neuroendocrine and somatostatin receptor cancers have been an ongoing subject of investigation, and the RPT agents targeting these cancers have probably reached maturity with the FDA approval of 177Lu-labelled DOTATATE.
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Antibodies to a variety of tumour-associated targets may be raised, including leukaemia-associated and lymphoma-associated targets (for example, CD20, CD45 and CD33), targets expressed on solid-tumour cancer cells (for example, carcinoembryonic antigen (CEA), prostate-specific membrane antigen (PSMA) and GD2) and targets expressed on their supporting microenvironment (for example, fibroblast activation protein-α (FAPα)). AML, acute myelogenous leukaemia; APC, antigen-presenting cell; BAFF-R, B cell-activating factor receptor; CAIX, carbonic anhydrase 9; DR, death receptor; sIg, secretory immunoglobulins. Adapted from ref.305, Springer Nature Limited. 2ff7e9595c
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