Development of Targeted Alpha Therapy from Bench to Bedside.

This review briefly describes recent promising developments of alpha emitter labelled compounds for targeted alpha therapy of bladder cancer, brain tumours, neuroendocrine tumours, and prostate cancer.

Radioinmunoterapia en los linfomas no Hodgkin: desarrollo histórico y estado actual / Radioimmunotherapy for non-Hodgkin lymphomas: historical development and currents

La radioinmunoterapia (RIT) es un nuevo enfoque terapéutico en el tratamiento de los linfomas. En febrero de 2002, tras varios años de desarrollo de diversos compuestos radioinmunoterápicos se aprobó, primero en Estados Unidos y posteriormente en Europa, el 90Y-ibritumomab tiuxetan (Zevalin®, Y2B8) para el tratamiento de los linfomas de bajo grado o linfomas B transformados, en recaída o refractarios. El 90Y-ibritumomab tiuxetan utiliza el anticuerpo monoclonal antiCD20 y la emisión β del 90Y frente a las células B malignas. Los ensayos clínicos han demostrado su eficacia, observándose respuesta clínica en un rango del 80 %. Este producto se encuentra disponible en Europa, con una administración simplificada, para el tratamiento de la recaída en el linfoma folicular. En EE.UU. se ha aprobado posteriormente un antiCD20 similar con efecto radioterápico, el 131I tositumomab. Se están realizando estudios prometedores para ampliar las indicaciones de la RIT, como son en la consolidación, como parte del trasplante o en otros tipos histológicos, encontrándose algunos ya finalizados y otros en curso. La RIT se ha mostrado como una terapia complementaria efectiva y clínicamente relevante en los pacientes con linfoma, introduciendo a la Medicina Nuclear en el tratamiento de los linfomas

Radioimmunotherapy treatment for lymphoma is a novel targeted therapeutic approach. Several years of development of radioimmunotherapeutic compounds came to fruition in February of 2002 when 90Y-ibritumomab tiuxetan (Zevalin™, Y2B8) was approved in the USA and later in Europe, for the treatment of relapsed or refractory, low grade or transformed B-cell lymphoma in the USA. 90Y-ibritumomab tiuxetan utilizes a monoclonal anti-CD20 antibody to deliver β -emitting yittrium-90 to the malignant B-cells. Clinical trials have demonstrated its efficacy, with observed clinical responses in the 80 % range. This product has become available in Europe, with simplified administration, for the treatment of relapsed follicular lymphoma. A similar anti-CD20 radiotherapeutic compound, 131I-tositumomab, was subsequently approved in the USA. Promising studies exploring expanded applications of radioimmunotherapy as consolidation, as part of transplant, or in other histologic types have been recently completed or are under way. Radioimmunotherapy has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma, bringing the Nuclear Medicine into lymphoma therapeutics

Radioimmunotherapy for non-Hodgkin's lymphomas: a historical perspective.

One of the most promising therapeutic approaches currently under investigation for low-grade non-Hodgkin's lymphoma is the administration of monoclonal antibodies that recognize tumor-associated antigens. These antibodies can be used either in unmodified form or conjugated to cytotoxic drugs, toxins, or radionuclides. To date, the most promising of the immunoconjugates are radiolabeled antibodies. Radioimmunotherapy is an attractive approach because radiolabeled antibodies are effective even in the face of defective host immune effector function, antigen-negative variants, and poor penetration of the antibody into tumors. Iodine-131-and Yttrium-90-conjugated antibodies have shown superior response rates compared with unconjugated antibodies and have produced complete responses in 15% to 40% of treated patients. A variety of treatment approaches are currently being investigated, including administering radiolabeled antibodies in combination with chemotherapy and administering myeloablative doses with stem-cell rescue. This latter strategy has yielded complete remissions in the majority of treated patients, some durable for more than 5 years.

History of antibody therapy for non-Hodgkin's lymphoma.

Monoclonal antibodies (mAbs) were the first successful targeted therapy for cancer. In contrast to the nonspecific nature of most chemotherapy, antibodies bind with high specificity to cell-surface antigens, resulting in targeted killing of malignant cells, relative sparing of normal tissues, and low toxicity. Antibody therapy has undergone substantial development since Ehrlich's notion of a "magic bullet," in 1890. It was not until the 1970s, however, that mAbs became viable as therapeutic tools and clinical studies showed them to be effective. The results were most impressive in hematologic malignancies, especially B-cell non-Hodgkin's lymphoma. In 1997, rituximab (Rituxan; Genentech Inc, South San Francisco, CA, and Biogen Idec Inc, Cambridge, MA) became the first mAb approved by the US Food and Drug Administration for use in the treatment of cancer. The first approval for a radiolabeled antibody to treat cancer was in 2002 for (90)Y ibritumomab tiuxetan (Zevalin; Biogen Idec). This is a conjugate of an anti-CD20 mAb (ibritumomab, the murine parent of rituximab) with the beta-emitter radionuclide (90)Y. (90)Y ibritumomab tiuxetan has been shown to be safe and effective in the indicated patient population. Other radioimmunoconjugates are being investigated for the treatment of non-Hodgkin's lymphoma, as are several immunotoxins. This article reviews important events in the development of mAb therapy and radioimmunotherapy for B-cell non-Hodgkin's lymphoma.