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Application of the nuclear approach for the detection of inherited diseases is an important goal for nuclear medicine and will likely result in an important breakthrough, which will, hopefully, lead to improved diagnoses of genetic defects and objective evaluations of the efficacy of therapeutic strategies. Although still largely in the research realm, molecular imaging is in the process of emerging as a vital component of the diagnosis of disease and monitoring of the therapy. The clinical research in nuclear medicine has made major advancements in the direction of molecular medicine and targeted therapy. In the past few years, exponential achievements have been accomplished in the development of molecular nuclear imaging agents, as described below.

Hypoxia plays a critical role in tumor development and aggressiveness and is an important prognostic factor for resistance to antineoplastic treatments; therefore, it is required to measure the hypoxic level of tumor for a favorable outcome. The pretherapy information on the oxygenation status of a tumor microenvironment should also have implications for treatment selection. A diffuse distribution of hypoxia in a tumor might suggest a benefit from a systemic approach, such as a hypoxic cell cytotoxin, tirapazamine, or antigrowth factor drugs to combat the limitations of hypoxia. Alternatively, a more focal hypoxia might benefit from a local/regional approach, such as intensity-modulated radiation therapy-based radiation dose escalation to the hypoxic subvolume. This review anticipates that (18)F-FMISO ((18)F-fluoromisonodazole) and (64)Cu-ATSM-positron emission tomography (PET) will prove useful for selecting individual patients for the most appropriate treatment. The advent of new radiotracers has allowed noninvasive assessment of hypoxia, with the most extensively investigated and validated PET radiotracer for hypoxia to date being (18)F-FMISO. This article discusses the relevance and biology of hypoxia in cells and organ systems and reviews the laboratory and clinical applications of (18)F-FMISO and other agents in oncology.

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This synopsis attempts to summarize progress made in radioimmunotherapy (RIT) by the end of the 20th century addressing the problems, possible solutions, and recent developments. The reduction of minimal residual disease in an adjuvant setting appears to be a feasible goal for RIT utilizing short-range alpha-emitters. RIT has been more successful in the radiosensitive hematologic malignancies, for example lymphomas and leukemias as compared with small solid tumors. Several radiopharmaceuticals seem near approval for RIT in patients with non-Hodgkin's lymphoma (NHL) as therapeutic responses, including complete responses, are common. Obstacles to successful RIT have been recognized and strategies to overcome these hurdles and to improve efficacy are continuously being developed resulting in encouraging outcome particularly with locoregional routes of administration in solid tumors. Systemic RIT for solid tumors will need manipulating the tumor-host to improve the tumor uptake and retention of radioimmunoconjugates (RICs). The utilization of radiometals, stable chelators, biodegradable linkers and bone marrow transplantation should be able to deliver the radiation dose required for successful treatment. In conjunction with additional synergistic agents, RIT is likely to have a great impact on the treatment of solid tumors. The ability to generate new constructs, such as bivalent antibodies or fusion proteins incorporating two different functional proteins opens exciting opportunities for new therapeutic modalities. These developments will hopefully offset the impediments to the successful use of RIT.