Microdosimetric concepts in radioimmunotherapy

Abstract

In microdosimetry particular emphasis is placed on the stochastic fluctuation of dose in small target volumes such as individual cell nuclei or chromatin fiber, and their relevance to radiobiologic toxicity. Thus microdosimetry is intimately associated with models of radiation action. There are three principal areas where microdosimetry has been applied: (1) radiation protection, (2) high LET radiotherapy, e.g., neutron therapy, and (3) incorporated radionuclides, and in this latter category the importance of microdosimetry to the radiobiology of radiolabeled antibodies is becoming increasingly recognized. The objective of microdosimetry is the complete characterization of energy deposition within all target volumes throughout the tissue of interest. The importance and relevance of this pursuit will depend upon the properties of the radionuclide emissions and the spatial distribution of the radionuclide relative to the target volumes. If the distribution of internal emitters within both malignant and normal tissue is uniform, the application of microdosimetry to radioimmunotherapy (RIT) is limited to alpha-emitters and Auger emitters. Under such circumstances the traditional MIRD formalism for the evaluation of tumor and tissue doses from the commonly used beta-emitters is entirely adequate. This, however, is rarely the case. When the distribution of radiolabeled antibody is nonuniform, techniques of dose averaging over volumes greater in size than the individual target volumes can become inadequate predictors of the biological effect. The concepts, methods, and realm of applicability of microdosimetry within the field of radioimmunotherapy are emphasized in this paper.

The α-Camera: A Quantitative Digital Autoradiography Technique Using a Charge-Coupled Device for Ex Vivo High-Resolution Bioimaging of α-Particles

“…Thus, micro-and small-scale dosimetry based on true radionuclide tissue distributions can be important tools to predict and explain normal-organ toxicities and tumor responses. Several studies (9)(10)(11)(12) have emphasized the need for such tools.…”

Radionuclide targeting and dosimetry at the microscopic level: the role of microautoradiography

“…The limitation must be accepted, of course, that the quantity and quality of the dose to DNA itself is the true determinant of cytotoxicity; this level of resolution is beyond microautoradiography. While knowledge of the abundance, energy and range of various emissions from radionuclides in tissue permits calculation of radiation dose to cell nuclei from various model tissue and cellular distributions of radionuclides within cells [4][5][6][7][8][9][10], the actual cellular/subcellular distribution must be known in order to calculate the actual dose to the nucleus. Microautoradiographic techniques have the potential to generate the necessary distribution data since the spatial relationship of source and target regions can be determined (to yield S-values), which may then be used in the same way as in macroscopic dose modelling using the MIRD schema [8,9].…”

“…Several model frameworks for microdosimetry have appeared recently, applicable at various levels from the subcellular (1 gin) to the lower limit of scanner resolution (several ram) [4][5][6][7][8][9][10]. Various radionuclides are modelled, including Auger emitting diagnostic nuclides, fl-emitters with a range of energies, and g-emitters, in the context of various cell and tissue geometries and various limiting model microscopic distributions.…”

Preparation of Rh[16aneS4-diol]211At and Ir[16aneS4-diol]211At Complexes as Potential Precursors for Astatine Radiopharmaceuticals. Part I: Synthesis

“…Additionally, its electron capture decay branch gives rise to Po K X-rays making 211 At easy to follow with standard nuclear detection devices including γ cameras for imaging (5). Dosimetry calculation and preclinical testing of compounds labeled with 211 At have indicated a significant therapeutic potential, at least in certain settings, relative to the use of radionuclides that emit particles with low linear energy transfer (6)(7)(8)(9)(10)(11)(12).…”