Molecular and cellular radiobiological effects of Auger emitting radionuclides

Abstract

Although the general radiobiologic principles underlying external beam therapy and radionuclide therapy are similar, significant differences in the biophysical and radiobiologic effects from the two types of radiation continue to accumulate. Here, I will address the unique features that distinguish the molecular and cellular radiobiological effects of Auger electron-emitting radionuclides consequent to (1) the physical characteristics of the decaying atom and its subcellular localisation, (2) DNA topology and (3) the bystander effect. Based on these experimental findings, I postulate that the ability of track structural simulations as primary tools in modelling DNA damage and cellular survival at the molecular level would be greatly enhanced when these contributions are factored in.

Figure 1.

LET of electrons as function of their energy. Arrows indicate the range of electrons at each specified energy.

Figure 2.

Radiotoxicity of Auger electron emitters post-localisation within nuclei of mammalian cells as function of energy deposited in nucleus⁽³⁴⁾. IUdR and BrUdR: iodo- and bromo-deoxyuridines (thymidine analogues); I-AP: iodo-acetyl proflavine (DNA intercalator); Trans-Pt: trans-platinum (forms adducts with DNA).

Figure 3.

Inhibitory (¹²⁵IUdR) and stimulatory (¹²³IUdR) bystander effects consequent to decay of either Auger electron emitter within human tumours grown subcutaneously . in mice^{(41, 42)}.

Figure 4.

Therapeutic response of CA19.9 antigen in patient with intrathecal tumour following i.t. administration of MTX and ¹²⁵IUdR⁽⁵⁰⁾.

Figure 5.

(A) Planar image obtained 42 h after infusion of ¹²³IUdR into the hepatic artery of a patient with massive liver metastatic disease from colorectal cancer (residual radioactivity adsorbed in the subcutaneous port and in the intra-arterial catheter is visible-arrows). ¹²³IUdR is incorporated in several metastatic tumour lesions, primarily in the left lobe⁽⁵¹⁾. (B) Metabolic modulation of ¹²³IUdR uptake in liver metastases. Patients were imaged after hepatic artery infusion of ¹²³IUdR both under baseline conditions and following biochemical modulation obtained by premedication with 5-fluorouracil and folinic acid 1 week later⁽⁵²⁾.