Anti-Tumor Activity vs. Normal Cell Toxicity: Therapeutic Potential of the Bromotyrosines Aerothionin and Homoaerothionin In Vitro.

Novel strategies to treat cancer effectively without adverse effects on the surrounding normal tissue are urgently needed. Marine sponges provide a natural and renewable source of promising anti-tumor agents. Here, we investigated the anti-tumor activity of Aerothionin and Homoaerothionin, two bromotyrosines isolated from the marine demosponge Aplysina cavernicola, on two mouse pheochromocytoma cells, MPC and MTT. To determine the therapeutic window of these metabolites, we furthermore explored their cytotoxicity on cells of the normal tissue. Both metabolites diminished the viability of the pheochromocytoma cell lines significantly from a concentration of 25 µM under normoxic and hypoxic conditions. Treatment of MPC cells leads moreover to a reduction in the number of proliferating cells. To confirm the anti-tumor activity of these bromotyrosines, 3D-pheochromocytoma cell spheroids were treated with 10 µM of either Aerothionin or Homoaerothionin, resulting in a significant reduction or even complete inhibition of the spheroid growth. Both metabolites reduced viability of normal endothelial cells to a comparable extent at higher micromolar concentration, while the viability of fibroblasts was increased. Our in vitro results show promise for the application of Aerothionin and Homoaerothionin as anti-tumor agents against pheochromocytomas and suggest acceptable toxicity on normal tissue cells.

End-to-end test for fractionated online adaptive MR-guided radiotherapy using a deformable anthropomorphic pelvis phantom.

Objective.In MR-guided radiotherapy (MRgRT) for prostate cancer treatments inter-fractional anatomy changes such as bladder and rectum fillings may be corrected by an online adaption of the treatment plan. To clinically implement such complex treatment procedures, however, specific end-to-end tests are required that are able to validate the overall accuracy of all treatment steps from pre-treatment imaging to dose delivery.Approach.In this study, an end-to-end test of a fractionated and online adapted MRgRT prostate irradiation was performed using the so-called ADAM-PETer phantom. The phantom was adapted to perform 3D polymer gel (PG) dosimetry in the prostate and rectum. Furthermore, thermoluminescence detectors (TLDs) were placed at the center and on the surface of the prostate for additional dose measurements as well as for an external dose renormalization of the PG. For the end-to-end test, a total of five online adapted irradiations were applied in sequence with different bladder and rectum fillings, respectively.Main results.A good agreement of measured and planned dose was found represented by highγ-index passing rates (3%/3mmcriterion) of the PG evaluation of98.9%in the prostate and93.7%in the rectum. TLDs used for PG renormalization at the center of the prostate showed a deviation of-2.3%.Significance.The presented end-to-end test, which allows for 3D dose verification in the prostate and rectum, demonstrates the feasibility and accuracy of fractionated and online-adapted prostate irradiations in presence of inter-fractional anatomy changes. Such tests are of high clinical importance for the commissioning of new image-guided treatment procedures such as online adaptive MRgRT.

In the context of radiosurgery - pros and cons of rescanning as a solution for treating moving targets with scanned particle beams.

The treatment of mobile targets with scanned particle beams is challenging, and the effects of motion will be especially pronounced in hypo-fractionated treatment regimes due to the lack of statistical smoothing through fractionation and the prolonged delivery times per session. Therefore, motion mitigation techniques will play a major role for radiosurgery approaches. This article concentrates on the motion mitigation technique called rescanning. It alludes the existence of many scanning/rescanning flavors and raises awareness of the importance of an optimized flavor choice. Furthermore, it is discussed that rescanning can compensate for the lack of statistical wash-out, target dose conformity, however, will remain degraded. Therefore, especially in the context of radiosurgery, rescanning should be combined with other motion mitigation techniques like breath hold, gating and/or tracking.