Antibody-targeted radiation cancer therapy

Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1

“…is preferable in the treatment of large tumor masses such as those that occur with the SUDHL-1 model. In the clinical situation, this agent may eliminate nontargeted tumor cells through the crossfire effect emanating from neighboring antigen-bearing cells that have been targeted by the radiolabeled monoclonal antibody (28). Nevertheless, the use of ␤-emitting radionuclides is limited as the target mass decreases the benefit of the crossfire effect also decreases, whereas the potential for normal tissue damage increases (32).…”

“…However, such monoclonal antibodies have been largely ineffective with only a few exceptions in this arena. Arming of monoclonal antibodies with toxins or radionuclides to specifically target these cytotoxic agents to tumor cells provides a valuable augmentation of their therapeutic efficacy (28,37,38).…”

“…Among the ␣-emitters currently under investigation for use in radioimmunotherapy, 211 At is perhaps the most promising candidate for radioimmunotherapeutic applications on the basis of half-life (t 1/2 ϭ 7.2 h) considerations. In contrast, ␤-emitters such as 90 Y that act through crossfire may be preferable in the treatment of large tumor masses (28)(29)(30). In the clinical situation, this latter agent may eliminate nontargeted tumor cells through the crossfire effect emanating from neighboring antigen-bearing cells that have been targeted by the radiolabeled monoclonal antibody.…”

Therapeutic radionuclides in nuclear medicine: current and future prospects

“…Other potential applications of RIT include the treatment of breast, lung, pancreatic, stomach and ovarian carcinoma, neoplastic meningitis, leukemia, high-grade brain glioma, and metastatic colorectal cancer. Table 3 provides a summary of recently developed mAbs in advanced RIT trials and their status (Milenic et al, 2004). The clinical outcomes of these radiopharmaceuticals are discussed in the following section.…”

Rational Design and Generation of a Bimodal Bifunctional Ligand for Antibody-Targeted Radiation Cancer Therapy

“…5 The RIT system generally consists of three components: a radionuclide, a mAb, and a bifunctional ligand. 6 The modality requires the use of radioactive metals, which can be very toxic when deposited in vivo in normal tissue. Therefore, the success of clinical applications of RIT heavily depends on the performance of the bifunctional ligand that can rapidly form a stable complex, particularly with a relatively short-lived radioactive metal.…”