F-GE-180 PET provides a remarkably high tumour-to-background contrast in untreated and pretreated glioblastoma and shows tracer uptake even beyond contrast enhancement on MRI. To what extent F-GE-180 uptake reflects the tumour extent of human gliomas and inflammatory cells remains to be evaluated in future prospective studies with guided stereotactic biopsies and correlation of histopathological results.

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Poor target cell specificity is currently a major shortcoming of nanoparticles (NPs) used for biomedical applications. It causes significant material loss to off-target sites and poor availability at the intended delivery site. To overcome this limitation, we designed particles that identify cells in a virus-like manner. As a blueprint, we chose a mechanism typical of influenza A virus particles in which ectoenzymatic hemagglutinin activation by target cells is a mandatory prerequisite for binding to a secondary target structure that finally confirms cell identity and allows for uptake of the virus. We developed NPs that probe mesangial cells for the presence of angiotensin-converting enzyme on their surface using angiotensin I (Ang-I) as a proligand. This initial interaction enzymatically transforms Ang-I to a secondary ligand angiotensin II (Ang-II) that has the potential to bind in a second stage to Ang-II type-1 receptor (AT1R). The presence of the receptor confirms the target cell identity and triggers NP uptake via endocytosis. Our virus-mimetic NPs showed outstanding target-cell affinity with picomolar avidities and were able to selectively identify these cells in the presence of 90% off-target cells that carried only the AT1R. Our results demonstrate that the design of virus-mimetic cell interactive NPs is a valuable strategy to enhance NP specificity for therapeutic and diagnostic applications. Our set of primary and secondary targets is particularly suited for the identification of mesangial cells that play a pivotal role in diabetic nephropathy, one of the leading causes of renal failure, for which currently no treatment exists.

Background In this dosimetric study, a dedicated planning tool for single isocenter stereotactic radiosurgery for multiple brain metastases using dynamic conformal arc therapy (DCAT) was compared to standard volumetric modulated arc therapy (VMAT). Methods Twenty patients with a total of 66 lesions who were treated with the DCAT tool were included in this study. Single fraction doses of 15–20 Gy were prescribed to each lesion. Patients were re-planned using non-coplanar VMAT. Number of monitor units as well as V 4Gy , V 5Gy and V 8Gy were extracted for every plan. Using a density-based clustering algorithm, V 10Gy and V 12Gy and the volume receiving half of the prescribed dose were extracted for every lesion. Gradient indices and conformity indices were calculated. The correlation of the target sphericity, a measure of how closely the shape of the target PTV resembles a sphere, to the difference in V 10Gy and V 12Gy between the two techniques was assessed using Spearman’s correlation coefficient. Results The automated DCAT planning tool performed significantly better in terms of all investigated metrics ( p < 0.05), in particular healthy brain sparing (V 10Gy : median 3.2 cm 3 vs. 4.9 cm 3 ), gradient indices (median 5.99 vs. 7.17) and number of monitor units (median 4569 vs. 5840 MU). Differences in conformity indices were minimal (median 0.75 vs. 0.73) but still significant ( p < 0.05). A moderate correlation between PTV sphericity and the difference of V 10Gy and V 12Gy between the two techniques was found (Spearman’s rho = 0.27 and 0.30 for V 10Gy and V 12Gy , respectively, p < 0.05). Conclusions The dedicated DCAT planning tool performed better than VMAT in terms of healthy brain sparing and treatment efficiency, in particular for nearly spherical lesions. In contrast, VMAT can be superior in cases with irregularly shaped lesions.

The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.

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Viral infection patterns often rely on precisely coordinated sequences of distinct ligand–receptor interactions, leading in many cases to an outstanding target cell specificity. A successful mimicry of viral targeting strategies to create more site-specific nanoparticles (NPs) would therefore require particle–cell interactions to also be adequately controllable. In the present study, hetero-multivalent block-copolymer NPs present their attached ligands in a sterically controlled manner to create a sequential NP–cell interaction similar to the cell infiltration strategy of human adenovirus type 2. Targeting renal mesangial cells, particles therefore initially bind angiotensin II receptor type 1 (AT1r) on the cell surface via a structurally flexible AT1r antagonist. After a mandatory spatial approach, particle endocytosis is realized via binding of immobile αVβ3 integrins with a previously concealed secondary ligand, thereby creating a stepwise particle–cell interplay of primary NP attachment and subsequent uptake. Manufactured adenovirus-mimetic NPs show great avidity for both target motifs in vitro, leading to a substantial binding as well as subsequent cell uptake into target mesangial cells. Additionally, steric shielding of secondary ligand visibility leads to a highly controllable, sequential ligand–receptor interaction, whereby hetero-functional NPs activate mesangial cell surface integrins only after a successful prior binding to the AT1r. This stepwise cell identification significantly enhances mesangial cell specificity in co-culture assays with different off-target cells. Additionally, described NPs display excellent in vivo robustness by efficiently accumulating in the mesangium upon injection, thereby opening new paths for possible drug delivery applications.