[en] The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, noninvasive imaging by PET with [F-18]DPA-714 (TSPO) and [F-18]BR-351 (MMP) was used for the assessment of localization and quantification of the expression of TSPO and MMP. Imaging was performed in addition to established clinical imaging biomarker of active tumor volume ([F-18]FET) in conjunction with MRI. We hypothesized that each imaging biomarker revealed distinct areas of the heterogeneous glioma tissue in a mouse model of human glioma. Tracers were found to be increased 1.4-to 1.7-fold, with [F-18]FET showing the biggest volume as depicted by a thresholding-based, volumes of interest analysis. Tumor areas, which could not be detected by a single tracer and/or MRI parameter alone, were measured. Specific compartments of [F-18]DPA-714 (14%) and [F-18]BR-351 (11%) volumes along the tumor rim could be identified. [F-18]DPA-714 (TSPO) and [F-18]BR-351 (MMP) matched with histology. Glioma-associated microglia/macrophages (GAM) were identified as TSPO and MMP sources. Multi-tracer and multimodal molecular imaging approaches may allow us to gain important insights into glioma-associated inflammation (GAM, MMP). Moreover, this noninvasive technique enables characterization of the glioma microenvironment with respect to the disease-driving cellular compartments at the various disease stages. (authors)

[en] New molecular imaging approaches featuring the assessment of inflammatory processes in the vascular wall on top of existing anatomic and functional vessel imaging procedures could emerge as decisive tools for the understanding and prevention of cardiovascular events. In this respect imaging approaches addressing specific molecular and cellular targets in atherosclerosis are of high interest. This review summarizes the rationale and current status of nuclear imaging probes which possess high translational potential.

[en] Summary: The CGS 25966 derivative (R)-2-(N-Benzyl-4-(2-[¹⁸F]fluoroethoxy)phenyl-sulphonamido) -N-hydroxy-3-methylbutanamide [¹⁸F]9 represents a very potent radiolabelled matrix metalloproteinase inhibitor. For first human PET studies it is mandatory to have a fully automated radiosynthesis and a straightforward precursor synthesis available. The realisation of both requirements is reported herein. In particular, the corresponding precursor 8 was obtained in a reliable 7 step synthesis with an overall chemical yield of 2.3%. Furthermore, the target compound [¹⁸F]9 was prepared with a radiochemical yield of 14.8±3.9% (not corrected for decay).

[en] Introduction: The natural occurring vitamin biotin, also known as vitamin H or vitamin B₇, plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10^-15 M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [¹⁸F]4 for a potential application in positron emission tomography (PET). Methods: Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [¹⁸F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined. Results: Compound [¹⁸F]4 was obtained from precursor compound 3 with an average specific activity of 16 GBq/μmol within 45 min and a radiochemical yield of 45 ± 5% (decay corrected). [¹⁸F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [¹⁸F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination. Conclusion: An efficient synthesis for [¹⁸F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [¹⁸F]4.

[en] The CGS 27023A derivative (R)-2-(N-((6-fluoropyridin-3-yl) methyl)-4-methoxyphenyl-sulphonamido)-N-hydroxy-3-methylbutanamide 1a was identified as a very potent matrix metalloproteinase inhibitor. Here, we describe a one-step radiosynthesis of the target compound [¹⁸F]1a. The syntheses of [¹⁸F]1a resulted in a radiochemical yield of 12.1±5.9% (decay-corrected), a radiochemical purity of 98.8±0.6%, and a specific activity of 39±27 GBq/μmol at the end of synthesis within 160±18 min from the end of radionuclide production (n=5). Initial small-animal PET studies in wild-type mice (C57/BL6) showed no unfavourable tissue accumulation of [¹⁸F]1a