ABSTRACT
Proton therapy (PT) is a treatment with high dose conformality that delivers a highly-focused radiation dose to solid tumors. Targeted radionuclide therapy (TRT), on the other hand, is a systemic radiation therapy, which makes use of intravenously-applied radioconjugates. In this project, it was aimed to perform an initial dose-searching study for the combination of these treatment modalities in a preclinical setting. Therapy studies were performed with xenograft mouse models of folate receptor (FR)-positive KB and prostate-specific membrane antigen (PSMA)-positive PC-3 PIP tumors, respectively. PT and TRT using 177Lu-folate and 177Lu-PSMA-617, respectively, were applied either as single treatments or in combination. Monitoring of the mice over nine weeks revealed a similar tumor growth delay after PT and TRT, respectively, when equal tumor doses were delivered either by protons or by ߯-particles, respectively. Combining the methodologies to provide half-dose by either therapy approach resulted in equal (PC-3 PIP tumor model) or even slightly better therapy outcomes (KB tumor model). In separate experiments, preclinical positron emission tomography (PET) was performed to investigate tissue activation after proton irradiation of the tumor. The high-precision radiation delivery of PT was confirmed by the resulting PET images that accurately visualized the irradiated tumor tissue. In this study, the combination of PT and TRT resulted in an additive effect or a trend of synergistic effects, depending on the type of tumor xenograft. This study laid the foundation for future research regarding therapy options in the situation of metastasized solid tumors, where surgery or PT alone are not a solution but may profit from combination with systemic radiation therapy.
ABSTRACT
PURPOSE: To investigate a balanced steady state free precession sequence (b-SSFP) under a large range of conditions and to compare its performance with other types of gradient echo sequences for dynamic imaging. MATERIALS AND METHODS: Balanced turbo field echo (b-TFE; Philips Medical Systems, Best, The Netherlands) was investigated in vitro at a range of T2/T1 along with T1-contrast enhanced turbo field echo (T1-TFE) and turbo field echo (TFE) so that a comparison could be made. Performance was quantified in terms of the initial slope of the signal-to-noise ratio (SNR) vs. 1/T1 curve (sensitivity) and the range of 1/T1 before signal saturation (contrast dynamic range [CDR]). RESULTS: The b-TFE sequence was found to best perform, in terms of an optimal CDR, with a 90 degrees flip angle (FA), saturation preparation, and short inversion time. Using these parameters, the sensitivity was also higher than that of the TFE sequence and T1-TFE sequence under their respective optimal conditions. For detection of small changes in contrast agent concentration (0.0-0.1 mM), b-TFE was also found to be the sequence of choice, with optimized parameters as follows, 90 degrees FA, shortest TR/TE, and no magnetization preparation. The smallest matrices gave the highest signal sensitivity for all three sequences. CONCLUSION: The CDR of b-TFE was much narrower than that of T1-TFE but could be widened under optimized conditions. The sensitivity of the b-TFE technique was the highest of the three sequences under all conditions tested.