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Background Yttrium-90 dosimetry after radioembolization is reliant on accurate quantitative imaging of the microsphere deposition. Previous studies have focused on the correction of geometrical resolution effects. Purpose To uncover additional effects of respiratory motion. Material and Methods Mathematical models describing spherical tumors were formed and two blurring effects, limited geometrical resolution and respiratory motion, were simulated. The virtual images were used as basis for dose volume histogram estimations by convolving the radioactivity representations with a dose point kernel. Results For respiratory motion only, the largest errors were found for the smallest tumors and/or tumors with heterogeneous distribution of yttrium-90 microspheres. The deviations in max dose and dose to 25% and 50% of the tumor volume were estimated at 20-40%, 10-30%, and 0-30%, respectively. Additional blurring from geometrical resolution increased the errors to 55-75%, 50-60%, and 25-60%, respectively. Conclusion Respiratory motion contributes to underestimation of tumor dose and overestimation of normal tissue dose.

Introduction: Dynamic (18)F-FDG PET allows the study of glucose distribution in tissues as a function of time and space. Using pharmacokinetics, the temporal uptake pattern of (18)F-FDG may be separated into components reflecting perfusion and metabolism. Bevacizumab is an angiogenesis inhibitor which prevents the growth of new blood vessels, and may potentially lead to normalization of the blood circulation in the tumor. The purpose of the study was to explore the use of dynamic PET as a tool for monitoring treatment effect, reflected by changes in perfusion and metabolism., Materials and Methods: Twelve athymic nude mice, bearing the bilateral triple-negative human breast cancer xenograft MAS98.12 were treated with bevacizumab (5 mg/kg i.p.). Dynamic PET data was acquired prior to and 24 and 72 hours after treatment for 1 hour after injection of 10 MBq (18)F-FDG and fitted with a FDG two-tissue compartment model. The changes in the rate constants k1, k3, MRFDG and the vascular fraction νB were assessed. To evaluate the effect of treatment regimes, 30 mice, randomized in 5 groups, received either vehicle (0.9% NaCl), bevacizumab (5 mg/kg i.p.), doxorubicin (8 mg/kg i.v.) or bevacizumab and doxorubicin either together, or doxorubicin 24 hours after bevacizumab treatment. Tumor volume was measured twice a week., Results: The perfusion-related rate parameter k1 and the metabolic rate constant k3 decreased significantly 24 hours after treatment. This decrease was followed by an increase, albeit non-significant, at 72 hours post treatment. Doxorubicin given 24 hours after bevacizumab showed less antitumor effect compared to concomitant treatment., Conclusions: Dynamic PET can detect changes in tumor perfusion and metabolism following anti-angiogenic therapy in mouse xenograft models. Longitudinal dynamic PET, used to assess the efficacy of anti-angiogenic treatment, can identify the time frame of potential tumor vasculature re-normalization and allow optimal timing of supplementary therapy (radiation or chemotherapy).

Background: The majority of gastrointestinal stromal tumours (GISTs) contain oncogenic KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or platelet-derived growth factor-alpha (PDGFRA) receptor tyrosine kinase (TK) mutations and are initially, but only temporarily sensitive to TK inhibitors. The aim of this study was to establish and characterize a human GIST xenograft that could be used for evaluating various molecularly targeted therapies., Materials and Methods: GIST tissue from four patients was implanted under the skin of athymic nude mice. In one case a tumour line was established., Results: The xenograft showed characteristic GIST morphology and exhibited the same mutation profile as that of the patient., Conclusion: A human GIST xenograft with mutation in KIT exons 11 and 17 has been established and maintained in nude mice for 3 years (13 passages). This model will enable further studies on mechanisms of resistance, combination therapies and allow testing of novel targeted therapies.