This regular feature will enhance your knowledge of imaging technology in oncologic diagnosis, treatment, and evaluation. Tissue-Specific and Physiologic Nuclear Medicine Modalities The search for greater sensitivity for detecting small subclinical tumor deposits and improved specificity for distinguishing between malignant and benign masses has led to the development of techniques for linking radioactive labels to tumor-specific antibodies or tissue-specific biochemical agents. 1,2 Major progress is occurring as well in the development of nonspecific physiologic nuclear medicine modalities, most prominent among them being positron emission tomography (PET) and the recently adapted cardiac imaging agents. The current status of these new approaches is discussed below. Tumor-Specific Monoclonal Antibody Radioimmunoscintigraphy The early use of polyclonal murine antitumor antibodies for tumor localization has been succeeded by monoclonal antibody-based agents, although these, too, are of murine origin thus far. 3,4 The majority of agents under development are labeled with either a technetium 99m (99m Tc) or indium 111 (111 In) radiometal chelate. 5 These are popular because of their ease of preparation, their suitability for standard camera imaging, and the compatibility of their half-lives to the in vivo clearance of the antibody proteins. Whole antibodies and large fragments require the longer half-life of 111 In although this carries with it the disadvantage of high liver clearance, compromising imaging within and adjacent to the liver and, to a lesser extent, the gut. Smaller, more quickly cleared antibody Fab' fragments can be labeled advantageously with the shorter half-lived 99m Tc. Technetium is predominantly cleared by the kidneys, and the combination of fast biologic clearance of the antibody fragment and fast renal clearance of the radiolabel should result in less extensive background activity. Despite their theoretical appeal, the performance of these preparations can still be compromised by problems of poor tumor perfusion, low tumor cell-surface antigen representation, antigen heterogeneity, and nonspecific uptake. 5,6 One approach to reducing the confounding effects of high background activity has been the use of background subtraction techniques, as in the use of 99m Tc-labeled albumin in conjunction with 99m Tc-labeled antibody fragments; however, it is not clear whether improved specificity is in fact achieved. 7 A more recent elaboration on this approach has been the fusion of bone scan or computed tomography (CT) images with single-photon emission tomography (SPECT) images of the radioantibody scan. 8 Only limited experience with these approaches is yet reported. 9 An alternative approach attempts to apply the phenomenon of tumor antigen augmentation from exposure to cytokines such as interferon. 10,11 Here, too, the limited published clinical experience is inadequate to predict whether this phenomenon will be the basis of improved imaging performance. 12 A particularly intriguing approach, champ...
