Introduction (2002)

It has been more than two decades since the terms radioimmunodetection and radioimmunotherapy, representing the use of isotopic immunoconjugates for imaging and therapy, respectively, were introduced into the literature.1, 2 But it has only been in the last few years that this methodology has become of interest to medical and radiation oncologists as a potential new modality of cancer therapy, mainly because good responses have been observed in hematologic tumors, such as non-Hodgkin lymphoma (NHL). This advance has been the subject of a number of recent reviews, as has progress in the radioimmunotherapy of other tumor types.3-9 Suffice it to say that we have reached a better understanding of the targeting antibodies and their isotopic conjugates, how to predict anatomic sites of tumors and determine doses of treatment, and the resulting toxicities and responses; and this greater understanding is in part reflected in the contents of these proceedings. A resurgence of interest in cancer radioimmunotherapy has also resulted from the success of unconjugated, or naked, monoclonal antibodies in cancer therapy, especially the introduction of CD20 and HER-2/neu antibodies in the treatment of NHL and breast cancer, respectively. It has been estimated that several hundred clinical trials of investigational antibodies with oncologic indications are underway in the U.S. Various forms of these antibodies are being investigated: unconjugated (or naked), drug conjugates, and radioimmunoconjugates. For many of these agents, including the two naked antibodies that have been approved for commercialization, these advances have been based more on empiric therapy results than on advances in the understanding of the agents' mechanisms of action. In the case of the CD33 antibody, recently licensed in the U.S. for the treatment of myeloid leukemia, the mechanism is related to the colicheamycin cytotoxic drug conjugated thereto. There has also been recent expectation that at least one radioimmunoconjugate of CD20 antibodies may be approved for the treatment of NHL, thus ushering in the era of radioimmunotherapy as a proven new cancer treatment modality. This would likely be a reassurance to all of the investigators who have been engaged in developing cancer radioimmunotherapy and who have shared their science so generously throughout the proceedings of this conference and former Conferences on Radioimmunodetection and Radioimmunotherapy of Cancer, which were initiated in 1978.10-16 Reviewing the current proceedings and those of the prior seven conferences, spanning over two decades, it is impressive how the concentration on animal model studies in the early years has been replaced by clinical studies, and how the clinical studies have advanced from pilot to pivotal trials. Almost more than any other cancer discipline, radioimmunotherapy has become a reality through the collaboration and merging of several clinical disciplines, from medical oncology to radiation/nuclear medicine, and through its intertwining with more basic subjects, such as immunology, radiochemistry, medical physics, and immunopharmacology. But radioimmunotherapy was not developed de novo. Instead, it was initiated through radioimmunodetection, or the imaging of cancer with radiolabeled antibodies. These efforts were based on basic studies, both preclinical and clinical, of antibodies, immune response, radiolabeling, pharmacokinetics, imaging procedures, and the target tumors and sites being imaged. Although a number of antibody-based diagnostic imaging agents were developed and even commercialized, none ever fulfilled expectations, since other radiological tools, such as positron emission tomography and helical computed tomography, have displaced them in many clinical settings. Nevertheless, these imaging agents and the science that went into their study and development have had direct application to the therapeutic use of antibodies in general and radioimmunoconjugates in particular. The proceedings of this conference, held in Princeton, New Jersey, from October 12 to October 14, 2000 (conventionally referred to as the “Princeton Conference”), comprised presentations on the latest advances in the diverse disciplines contributing to antibody targeting and therapy. The current supplement contains 24 articles that span the topics of radiation biology and chemistry, physics and dosimetry, preclinical targeting and therapy, and clinical radioimmunotherapy. Of particular clinical interest is the authoritative article by DeNardo et al. on the subject of choosing the optimal dose of any radioimmunoconjugate for therapy. Although the emphasis has been on antibody conjugates, advances in the use of radiopeptides are also included. These articles were presented at the conference in abridged form, then expanded to full length. The full-length articles were completed within about 6 months of their publication in this supplement. It has been a distinct pleasure for me to organize and conduct the Conference on Radioimmunodetection and Radioimmunotherapy of Cancer, and now edit the proceedings. Fortunately, a highly qualified program committee assisted me, offering their valu-able talents and suggestions. We succeeded in recruit-ing leaders in different subjects of this field to present their results and views. We were also favored by an interactive and interested audience from diverse medical and scientific disciplines. And we convened in an intimate, stimulating, and comfortable atmosphere that fostered good communication and camaraderie. Special thanks are due my cochairman, Professor Jean-François Chatal, of Nantes, France; the Program Committee; the sponsors; and, most importantly, the participants, most of whom return to this biennial meeting to share their science and renew their acquaintanceships. Finally, these conferences have run smoothly because of the talents and devotion of my assistant, Lois Gillespie, who has earned her retirement but will remain an anchor to us behind the scenes. I also thank Rosaleen Church, who helped prepare the proceedings for publication. We plan to hold the next conference, with an expanded venue that will include other forms of antibodies and immunoconjugates, on October 24–26, 2002.