Animal models for medical countermeasures to radiation exposure.

Since September 11, 2001, there has been the recognition of a plausible threat from acts of terrorism, including radiological or nuclear attacks. A network of Centers for Medical Countermeasures against Radiation (CMCRs) has been established across the U.S.; one of the missions of this network is to identify and develop mitigating agents that can be used to treat the civilian population after a radiological event. The development of such agents requires comparison of data from many sources and accumulation of information consistent with the "Animal Rule" from the Food and Drug Administration (FDA). Given the necessity for a consensus on appropriate animal model use across the network to allow for comparative studies to be performed across institutions, and to identify pivotal studies and facilitate FDA approval, in early 2008, investigators from each of the CMCRs organized and met for an Animal Models Workshop. Working groups deliberated and discussed the wide range of animal models available for assessing agent efficacy in a number of relevant tissues and organs, including the immune and hematopoietic systems, gastrointestinal tract, lung, kidney and skin. Discussions covered the most appropriate species and strains available as well as other factors that may affect differential findings between groups and institutions. This report provides the workshop findings.

The biological effectiveness of antiproton irradiation.

BACKGROUND AND PURPOSE: Antiprotons travel through tissue in a manner similar to that for protons until they reach the end of their range where they annihilate and deposit additional energy. This makes them potentially interesting for radiotherapy. The aim of this study was to conduct the first ever measurements of the biological effectiveness of antiprotons. MATERIALS AND METHODS: V79 cells were suspended in a semi-solid matrix and irradiated with 46.7MeV antiprotons, 48MeV protons, or (60)Co gamma-rays. Clonogenic survival was determined as a function of depth along the particle beams. Dose and particle fluence response relationships were constructed from data in the plateau and Bragg peak regions of the beams and used to assess the biological effectiveness. RESULTS: Due to uncertainties in antiproton dosimetry we defined a new term, called the biologically effective dose ratio (BEDR), which compares the response in a minimally spread out Bragg peak (SOBP) to that in the plateau as a function of particle fluence. This value was approximately 3.75 times larger for antiprotons than for protons. This increase arises due to the increased dose deposited in the Bragg peak by annihilation and because this dose has a higher relative biological effectiveness (RBE). CONCLUSION: We have produced the first measurements of the biological consequences of antiproton irradiation. These data substantiate theoretical predictions of the biological effects of antiproton annihilation within the Bragg peak, and suggest antiprotons warrant further investigation.

Investigations of a minimally invasive method for treatment of spinal malignancies with LINAC stereotactic radiation therapy: accuracy and animal studies.

PURPOSE: A new method for stereotactic irradiation of spinal malignancies is presented, with evaluations of the theoretic and practical limitations of localization accuracy and the implementation of the method in swine. MATERIALS AND METHODS: In a percutaneous procedure, a minimum of three small (1.7-mm-diameter) titanium markers are permanently affixed to a vertebra. Markers are localized on biplanar radiographs while isocenter positions are determined on CT. An external fiducial frame defines a three-dimensional coordinate system through the patient. Radiographs coupled with a rigid body rotation algorithm account for daily differences in patient position. Phantom studies were used to verify theoretic uncertainty calculations from a simulation program. A swine model was used to evaluate the difficulty and duration of the implant technique, the suitability of the vertebral process as an implant site, vertebral motion due to normal respiration, and the ability to target one vertebra with markers in an adjacent vertebra. RESULTS: Theoretic accuracy studies confirmed that localization accuracy is a function of marker separation. Phantom studies involving 296 measurements showed that individual implants could be localized within +/-0.25 mm. The largest targeting error observed in 3,600 measurements of 100 implant configurations was 1.17 mm. The implant procedure took 5-10 minutes per site. No significant migration of implants was observed up to 35 days postimplantation, and respiratory motion had no detectable influence on vertebral position. Adjacent vertebrae may be useful for targeting one another with a small sacrifice in localization accuracy. CONCLUSIONS: The use of implanted markers for localization of spinal malignancies has potential for applications in stereotactic radiotherapy. Phantom measurements suggest that localization accuracy similar to intracranial stereotactic radiotherapy techniques is achievable. Swine studies suggest that the implant technique is expedient and feasible for tumor targeting purposes.