Principles of molecular targeting for radionuclide therapy

William C. Eckelman, Marie Boyd, Robert J. Mairs

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)


Molecular targeting requires assessing several factors that come into play such as the location of the target, the choice of radionuclide, the inertness of the bifunctional chelate and stability of the covalently bound halogens, matching the residence time in the tumor with the physical half-life of the radionuclide, the scale and scope of the disease, and the absorbed dose sensitivity of the targeted tumor compared to normal tissue. The principles of molecular targeting are well established, but a paradigm shift from designing a medium-affinity radiotracer used to determine target density to designing a high-affinity, hightarget density radioligand to maximize the target-to-nontarget ratio should increase the probability of detecting lesions smaller than the instrument resolution. Developing and validating a therapeutic radiopharmaceutical for a single target is necessary, but often not sufficient to produce a toxic event because of other mechanisms that are only partially understood. These include nontargeted effects due to radiation emitted from neighboring, targeted cells as well as bystander effects produced by the cellular processing of radiation not necessarily impinging on DNA. Both of these indirect consequences of cellular radiation could make a substantial contribution to the efficacy of targeted radionuclide therapy. These mechanisms should be exploited to optimize the efficacy of targeted radiotherapy and overcome the inefficiency of tumor control due to nonuniform distribution of radiation dose. The design approach to take advantage of the indirect consequences of cellular radiation depends heavily on further elucidation of the indirect effect. The successful combination of these two should lead to more effective nuclear radiotherapy.

Original languageEnglish
Title of host publicationNuclear Oncology
Subtitle of host publicationFrom Pathophysiology to Clinical Applications
EditorsH. William Strauss, Giuliano Mariani, Duccio Volterrani, Steven M. Larson
Place of PublicationCham, Switzerland
PublisherSpringer International Publishing AG
Number of pages31
ISBN (Print)9783319262345, 9783319262369
Publication statusPublished - 16 Nov 2017


  • alpha particles
  • auger electrons
  • beta particles
  • bystander effects
  • double-strand breaks
  • molecular targeting
  • residence time
  • theranostics
  • therapeutic radionuclides

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