"Recently, another study indicated that trastuzumab pharmacokinetics and organ distribution can also be heavily affected by an extensive tumor load . Therefore, a study with a more patient-tailored trastuzumab dosing schedule on the basis of tumor volume in addition to bodyweight should be considered in the future. "
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) imaging with radiolabeled monoclonal antibodies has always been a dynamic area in molecular imaging. With decay half-life (3.3 d) well matched to the circulation half-lives of antibodies (usually on the order of days), (89)Zr has been extensively studied over the last decade. This review article will give a brief overview on (89)Zr isotope production, the radiochemistry generally used for (89)Zr-labeling, and the PET tracers that have been developed using (89)Zr. To date, (89)Zr-based PET imaging has been investigated for a wide variety of cancer-related targets, which include human epidermal growth factor receptor 2, epidermal growth factor receptor, prostate-specific membrane antigen, splice variant v6 of CD44, vascular endothelial growth factor, carbonic anhydrase IX, insulin-like growth factor 1 receptor, among others. With well-developed radiochemistry, commercial availability of chelating agents for (89)Zr labeling, increasingly widely available isotope supply, as well as successful proof-of-principle in pilot human studies, it is expected that PET imaging with (89)Zr-based tracers will be a constantly evolving and highly vibrant field in the near future.
[Show abstract][Hide abstract] ABSTRACT: The concept of monoclonal antibodies (mAbs) as pharmacotherapeutics was validated in the mid-1980s with the successful clinical development of the fully murine mAb muromonab-CD3 for prevention of acute organ rejection. However, clinical applications of fully murine mAbs are restricted, owing to the high incidence of serious immune-mediated side effects, particularly upon repeated exposure. The rate and severity of immune-mediated toxicities of these agents were significantly attenuated by the development of mouse/human chimeric, fully human, and humanized mAbs. These refinements in molecular structure allowed repeated, long-term administration, where therapeutically warranted, which, in turn, broadened the scope of indications for this class of therapy. Presently, numerous mAbs are approved or are undergoing clinical evaluation for treatment of oncologic and chronic inflammatory diseases. The current experimental development landscape spans respiratory, metabolic, and central nervous system disorders as well as infectious disease. A consequence of the expanding numbers of mAb indications is concomitant administration of these agents with established small molecule pharmacotherapies, which necessitates a comprehensive understanding of mAb-small molecule drug interactions as well as mAb-mAb interactions. Current knowledge indicates that mAbs do not elicit a direct effect on the metabolic/clearance pathways for small molecular therapeutics. However, the immunomodulatory properties of mAbs can indirectly alter clearance of certain small molecule entities through the attenuation of noncatabolic enzymatic pathways.
[Show abstract][Hide abstract] ABSTRACT: With current testing strategies, the number of novel targeted anticancer agents will exceed our drug selection capacity. Molecular imaging is a powerful additional tool that can assist us in selecting effective drugs and help patients benefit from targeted agents. Moreover, measurement of the functional effects of such targeted agents could permit dynamic tuning of treatment selection at the earliest time point at which loss of functional effects is observed. Cancer Discovery; 1(1); 25-8. (C) 2011 AACR.
Cancer Discovery 06/2011; 1(1):25-8. DOI:10.1158/2159-8274.CD-11-0051 · 19.45 Impact Factor
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