On 5–7 July 2007 a 6th international symposium on biophysical aspects of Auger processes celebrated 20 years of scientific gatherings to discuss the physical, molecular, cellular and medical consequences of Auger-electron cascades. Formerly begun in 1987, the roots of the symposia go back to a conference organized by Ludwig Feinendegen in 1975 at the nuclear research laboratories in Julich, during which many of the themes for continued discovery were established. Tracking the venues of International Congresses of Radiation Research, the group has held its meetings in Oxfordshire (Charney Bassett), Amherst (University of Massachusetts), Lund (on two occasions), and Melbourne (Peter MacCallum Cancer Centre).
The 2007 meeting, held in Boston at Harvard Medical School, brought together some 50 scientists working actively in the field. As has become traditional, the conference began with a report on progress since the previous symposium as seen through the literature. Ably presented by Roger Howell, the group was led through a comprehensive and heuristically organized review of the field, highlighting the essence of more than 150 papers. Professor Howell predicted increasing utility for Auger cascades in the study of DNA damage and repair, as probes of molecular structure, and as contributors to the treatment of disease.
There followed a series of presentations, most of which are published in this issue of International Journal of Radiation Biology.
In the study of molecular effects, a central role for coulombic explosion and charge neutralization has again been raised, and the importance of DNA topology on double-strand break (DSB) yields demonstrated. The dependence of DSB on the distance of radio-iodine from the DNA helix has been further explored and appears to agree with theoretical calculations at short distances but not at long ones. A new iodine isotope, 124I, now joins 123I and 125I as an Auger-electron emitter of interest while also serving as an imaging radionuclide.
In terms of fundamental properties in Auger decay, we were told that much is yet to be learned about the mechanism of emissions, the number and properties of the emitted electrons, and the role of coulombic explosion. Computer models of radiation-induced DNA damage have been used to reveal mechanisms, interpret experimental findings, testing hypotheses and predicting radiation risks. Simulated damage to plasmid DNA has found good qualitative but inexact quantitative correlation with experimental findings.
Soft X-rays continue to be used to produce Auger decay. The energy dependences observed led investigators to believe that the sugar moiety is the fragile site for DNA damage. On the other hand, no enhancement in treatment of experimental brain tumors could be found with iodine-enhanced synchrotron stereo tactic radiotherapy.
Variations in response to intranuclear Auger cascades have been observed in different cell types. Most surprising is the radio-resistance to be found in human embryonic stem cells. Of the 1500 genes found up- or down-regulated on exposure of skin cells to Auger decay, most are concerned with cell cycle inhibition and DNA repair. Despite the syncitial properties of testicular tissues, no bystander-effect could be demonstrated with intranuclear iodine-125 labeling.
One approach to the use of Auger electron-emitters for targeted radionuclide therapy aims at cell surface receptors with subsequent translocation to the nucleus. Two such targets are HER2/neu and EGFR. Indium-111 labeled monoclonal antibodies to both are translocated to the nucleus of receptor positive cells, causing double-strand breaks and cytotoxicity. For ligands that are not self-locating to the nucleus, the use of Tat peptides as leaders is an alternate approach to the creation of a therapeutic product. Lastly, one example of the locoregional use of a 125I-labeled compound for therapy of neoplastic meningitis in a cancer patient was described with promising results.
These and other findings are elaborated in the papers included in this issue. While much has been accomplished, still more remains to be done. We anticipate another yeasty symposium in 2011 returning, after 36 years, to Julich.
We are most grateful to Alice Carmel for her many efforts in organizing the symposium and seeing that it ran smoothly. We also thank members of the Scientific Committee (R.W. Howell, R.F. Martin, H. Nikjoo, E. Pomplun, M. Terrissol, R. Wantannbe, and L. Yasui) for help in planning the conference, Pavel Popisil in being a webmaster, and, together with many others, in reviewing the manuscripts.