Joseph M. Baisden

Semiconductor nanoparticles as energy mediators for photosensitizer-enhanced radiotherapy.

PURPOSE It has been proposed that quantum dots (QDs) can be used to excite conjugated photosensitizers and produce cytotoxic singlet oxygen. To study the potential of using such a conjugate synergistically with radiotherapy to enhance cell killing, we investigated the energy transfer from megavoltage (MV) X-rays to a photosensitizer using QDs as the mediator and quantitated the enhancement in cell killing. METHODS AND MATERIALS The photon emission efficiency of QDs on excitation by 6-MV X-rays was measured using dose rates of 100-600 cGy/min. A QD-Photofrin conjugate was synthesized by formation of an amide bond. The role of Förster resonance energy transfer in the energy transferred to the Photofrin was determined by measuring the degree of quenching at different QD/Photofrin molar ratios. The enhancement of H460 human lung carcinoma cell killing by radiation in the presence of the conjugates was studied using a clonogenic survival assay. RESULTS The number of visible photons generated from QDs excited by 6-MV X-rays was linearly proportional to the radiation dose rate. The Förster resonance energy transfer efficiency approached 100% as the number of Photofrin molecules conjugated to the QDs increased. The combination of the conjugate with radiation resulted in significantly lower H460 cell survival in clonogenic assays compared with radiation alone. CONCLUSION The novel QD-Photofrin conjugate shows promise as a mediator for enhanced cell killing through a linear and highly efficient energy transfer from X-rays to Photofrin.

Helical tomotherapy simultaneous integrated boost provides a dosimetric advantage in the treatment of primary intracranial tumors

Abstract Objective: The research quantitatively evaluates the dosimetric advantage of a helical tomotherapy (HT) intensity-modulated radiation therapy simultaneous integrated boost (SIB) compared to a conventional HT sequential (SEQ) boost for primary intracranial tumors. Methods: Hypothetical lesions (planning target volumes or PTVs) were contoured within computed tomography scans from normal controls. A dose of 50 Gy was prescribed to the larger PTV1, while the boost PTV2 received a total of 60 Gy. HT SEQ and HT SIB plans were generated and compared. We evaluated the mean brain dose, the volume of normal brain receiving 45 Gy (V45), the volume of normal brain receiving 5 Gy (V5), and the integral dose. In addition, patients who were treated with the HT SEQ technique were replanned with the HT SIB technique and compared. Results: The average reduction in mean brain dose with the HT SIB plan compared to the composite HT SEQ plan was 11·0% [standard error (SE): 0·5]. The reductions in brains V45 and V5 were 43·7% (SE: 2·3) and 3·9% (SE: 0·6), respectively. The reduction in the integral dose was 11·0% (SE: 0·5). When comparing the SIB plan to the first 50 Gy only of the SEQ plan, there was only a 2·5% increase in the mean brain dose and a 2·9% increase in brain V45. This increase was dependent on the relative volumes of PTV2 and PTV1. These results were confirmed for the patient plans compared. Conclusions: Treating primary brain tumors with the HT SIB technique provides significant sparing of normal brain parenchyma compared to a conventional HT SEQ boost.