Subcellular Targeting of Theranostic Radionuclides

Abstract

The last decade has seen rapid growth in the use of theranostic radionuclides for the treatment and imaging of a wide range of cancers. Radionuclide therapy and imaging rely on a radiolabeled vector to specifically target cancer cells. Radionuclides that emit β particles have thus far dominated the field of targeted radionuclide therapy (TRT), mainly because the longer range (μm–mm track length) of these particles offsets the heterogeneous expression of the molecular target. Shorter range (nm–μm track length) α- and Auger electron (AE)-emitting radionuclides on the other hand provide high ionization densities at the site of decay which could overcome much of the toxicity associated with β-emitters. Given that there is a growing body of evidence that other sensitive sites besides the DNA, such as the cell membrane and mitochondria, could be critical targets in TRT, improved techniques in detecting the subcellular distribution of these radionuclides are necessary, especially since many β-emitting radionuclides also emit AE. The successful development of TRT agents capable of homing to targets with subcellular precision demands the parallel development of quantitative assays for evaluation of spatial distribution of radionuclides in the nm–μm range. In this review, the status of research directed at subcellular targeting of radionuclide theranostics and the methods for imaging and quantification of radionuclide localization at the nanoscale are described.

Targeted Brain Tumor Radiotherapy Using an Auger Emitter

“…Here, we focus on PARP1-based radiotherapy with a more sporadically utilized type of radioactive emission: Auger radiation. Auger emitters are an extremely potent radioactive source for targeted radiotherapy, characterized by their greater linear energy transfer, incredibly short range, and ability to cause a complex, lethal DNA damage as compared to traditional X-rays or -particles (27)(28)(29)(30)(31)(32).…”

“…Previous attempts to use Auger emitters as cancer therapies have not been successful, due to the limited range of the radiation emitted and the difficulty of reliably delivering the lethal electrons close enough to the DNA target (< 100 Å) (31,(33)(34)(35).…”

Targeted brain tumor radiotherapy using an Auger emitter

“…Auger emitters are an extremely potent radioactive source for targeted radiotherapy, characterized by their greater linear energy transfer, incredibly short range, and ability to cause a complex, lethal DNA damage as compared to traditional X-rays or b-particles (27)(28)(29)(30). Previous attempts to use Auger emitters as cancer therapies have not been successful, due to the limited range of the radiation emitted and the difficulty of reliably delivering the lethal electrons close enough to the DNA target (< 100 Å) (31)(32)(33).…”

Development of a new database for Auger electron and X-ray spectra

“…Low-energy electrons can be provided by radioisotopes that emit Auger electrons as part of their electron capture and/or internal conversion decays. The possible use of Auger electrons in cancer therapy has been discussed extensively in the literature [1][2][3]. In order to use Auger electrons for medical applications, it is important to know their yields and energy distribution.…”