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[en] Full text of publication follows. The role of International Atomic Energy Agency (IAEA) is to promote pacific applications of nuclear energy and radioactivity that may help to improve the economic and social levels in Member States. In this respect, the improvement of national health care systems through the introduction of new diagnostic and therapeutic approaches developed within the field of nuclear medicine is one of its major goals. Finding effective cancer treatments is still at the forefront of IAEA projects due to the global impact of this disease. At the most fundamental level, cancer can be viewed as a perfect example of 'molecular disease' originating when the inner biochemical fabric of the cell is abnormally altered. It is exactly the complexity of this molecular machinery that makes the understanding and treatment of cancer so difficult. However, in the search for a consistent therapeutic approach, this basic molecular paradigm cannot be escaped. In this context, radionuclide therapy employing single-molecule radiolabelled substances still constitutes a promising tool for cancer treatment due to its intrinsic molecular nature. Radionuclide therapy is unique in its ability to deliver selectively to cancerous cells a therapeutic dose of radioactivity by means of rationally designed molecular carriers. Thus, a key advantage of molecular radionuclide therapy is that it does not need to achieve the full molecular picture, but just some relevant piece of the entire puzzle that may allow targeting selectively tumour cells. The major challenge is to find a perfect matching between the molecular properties of a radiolabeled agent and a relevant bio-molecular mechanism capable of uploading the required amount of radioactivity at the tumour site. In this respect, iodine-131 based therapy still remains a unique, unmatched example. IAEA is constantly promoting projects and scientific discussions on the applications of therapeutic radiopharmaceuticals in oncology. These programmes are pursued through different mechanisms such as the organization of Technical Projects, Coordinated Research Projects and Technical Meetings, and by supporting scientific conferences and symposia on selected topics. The ultimate goal is always to assist Member States in expanding their knowledge and favouring applications of effective target-specific radiopharmaceuticals that may provide a real benefit for the early detection and treatment of different type of cancers. (author)
[en] Background: As systemic control of high-risk neuroblastoma (NB) has improved, relapse in the central nervous system (CNS) is an increasingly recognized entity that carries a grim prognosis. This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT). Methods: A retrospective query identified 29 children with NB treated at Memorial Sloan-Kettering Cancer Center since 1987 who received RT for CNS relapse. At CNS relapse, 16 patients received CSI (median dose, 2160cGy), and 13 received focal RT. Of those who underwent CSI, 14 (88%) received intra-Ommaya (IO) radioimmunotherapy (RIT); one patient in the non-CSI cohort received IO-RIT. Results: Patient characteristics were similar between the groups. Time to CNS relapse was 20 and 17 months for the CSI and non-CSI cohorts, respectively. At a median follow-up of 28 months, 12 patients (75%) in the CSI group are alive without CNS disease, including two patients with isolated skeletal relapse. Another patient is alive without disease after a brain relapse was retreated with RT. Three patients died-one with no NB at autopsy, one of CNS disease, and one of systemic disease. The two patients who died of NB did not receive IO-RIT. All 13 patients in the non-CSI cohort died at a median of 8.8 months. Conclusions: Low-dose CSI together with IO-RIT provides durable CNS remissions and improved survival compared with focal RT and conventional therapies. Further evaluation of long-term NB survivors after CSI is warranted to determine the treatment consequences for this cohort.
[en] This article shows that radioimmunotherapy (RIT) was invented more than 30 years ago and at its beginning (between 1993 and 1997) results were quite modest: over a population of 300 patients and with all pathological indications being considered, the clinical effectiveness reached 2% of complete and partial responses and 3% of minor responses. The main cause of these poor results was the very large tumor burden in the majority of the patients which is now commonly recognized as not favorable for RIT efficiency. Consequently, in the clinical studies performed between 1997 and 2002, patients with smaller tumors were considered, higher activities were injected sometimes with stem cell rescue and, in a few studies RIT was associated with chemotherapy and especially with Taxol. The results of such studies, showed a significant clinical efficacy improvement. In the beginning of the 2000 years the situation of RIT has been rapidly progressing. Two radiolabeled antibodies (Bexxar and Zevalin) have been approved for the treatment of radiosensitive non-Hodgkin's lymphoma, thus illustrating the fact that RIT has come of age as a new therapeutic modality. Since then new technological approaches have been developed and clinically validated
[en] Molecular targeting may be defined as the specific concentration of a diagnostic or therapeutic tracer by its interaction with a molecular species that is distinctly present or absent in a disease state. Monoclonal antibody (mAb) is one of the successful agents for targeted therapy in cancer. To enhance the therapeutic effect. the concept of targeting radionuclides to tumors using radiolabeled mAbs against tumor-associated antigens, radioimmunotherapy, was proposed. The efficacy of radioimmunotherapy, however, has to be further optimized. Several strategies to improve targeting of tumors with radiolabeled mAbs have been developed, such as the use of mAb fragments, the use of high-affinity mAbs, the use of labeling techniques that are stable in vivo, active removal of the radiolabeled mAb from the circulation, and pretargeting strategies. Until now, however, there are many kinds of obstacles to be solved in the use of mAb for the targeted therapy. Major technical challenges to molecular targeting are related to the rapid and specific delivery of tracers to the target, the elimination of unwanted background activity, and the development of more specific targets to create a cytocidal effect. Further development of this field will be determined by success in solving these challenges
Purpose of ReviewRadioimmunotherapy (RIT) is the targeting of radiosensitive tumors through the use of monoclonal antibodies. The purpose of this review is to discuss the benefit and challenges of RIT. We appraise factors that determine optimal targeting of tumor such as choice of target, targeting antibody, and the associated radionuclide, as well as the current methods to potentiate RIT effect.
Recent FindingsRadioimmunotherapy has a well-established role in the treatment of hematological malignancies. Recent completed and current studies in the treatment of solid malignancies are however demonstrating good clinical response with acceptable toxicity profiles.
SummarySince its inception, improved molecular engineering and targeting of new molecules, the discovery of new potential tumor targets, and the incorporation of methods to potentiate effect and reduce toxicity, will probably see radioimmunotherapy becoming a more commonplace treatment in the management of both hematological and solid malignancies.
[en] A method is disclosed of treating solid tumor cancer in a living being by prolonging the time a therapeutically effective agent remains in the tumor. The method comprises the steps of selecting particles of an aggregated protein and injecting them interstitially into the tumor. The therapeutically effective agent selected from the group consisting of radioactive antibodies and radioactive growth factors is injected into the tumor either after the injection of the proteinaceous particles, or simultaneously. 7 figs