The search for novel image contrasts has been a major driving force in the magnetic resonance (MR) research community, in order to gain further information on the body’s physiological and pathological conditions.Chemical exchange saturation transfer (CEST) is a novel MR technique that enables imaging certain compounds at concentrations that are too low to impact the contrast of standard MR imaging and too low to directly be detected in MRS at typical water imaging resolution. For this to be possible, the target compound must be capable of exchanging protons with the surrounding water molecules. This property can be exploited to cause a continuous buildup of magnetic saturation of water, leading to greatly enhanced sensitivity.The goal of the present review is to introduce the basic principles of CEST imaging to the general molecular imaging community. Special focus has been given to the comparison of state-of-the-art CEST methods reported in the literature with their positron emission tomography (PET) counterparts.

Free energy changes of each elementary step involved in the formal hydride transfer (H(-)(T)) reactions (including the so-called "one-step" H(-)(T) and "multistep" H(-)(T) mechanisms) of the reduced nicotinamide adenine dinucleotide (NADH) models with various cations and quinones (17) were investigated either by direct thermodynamic measurements or by calculations from thermochemical cycles. Based on the energetic data thus derived, combined with kinetic observations (particularly kinetic isotope effects), the mechanistic characteristics of the NADH-mediated reductions were systematically analyzed. Practical guidelines that resulted from these analyses suggest that a mutistep mechanism (e(-)-H(*) or e(-)-H(+)-e(-)) would be followed if the energy gap of the initial electron transfer [DeltaG(e(-)(T))] between the NADH model compound and the reducing substrate is considerably smaller than the empirical critical limit of 1.0 V for an endothermic e(-)(T). In contrast, if DeltaG(e(-)(T)) is much greater than 1.0 V, a concerted one-step H(-)(T) may take place. The guideline also suggests that a "hybrid" mechanism is possible if the DeltaG(e(-)(T)) is in an intermdiate situation.

Despite the broad implications of the cannabinoid type 2 receptor (CB2) in neuroinflammatory processes, a suitable CB2-targeted probe is currently lacking in clinical routine. In this work, we synthesized 15 fluorinated pyridine derivatives and tested their binding affinities toward CB2 and CB1. With a sub-nanomolar affinity (K i for CB2) of 0.8 nM and a remarkable selectivity factor of >12,000 over CB1, RoSMA-18-d 6 exhibited outstanding in vitro performance characteristics and was radiofluorinated with an average radiochemical yield of 10.6 ± 3.8% (n = 16) and molar activities ranging from 52 to 65 GBq/μmol (radiochemical purity > 99%). [18F]­RoSMA-18-d 6 showed exceptional CB2 attributes as demonstrated by in vitro autoradiography, ex vivo biodistribution, and positron emission tomography (PET). Further, [18F]­RoSMA-18-d 6 was used to detect CB2 upregulation on postmortem human ALS spinal cord tissues. Overall, these results suggest that [18F]­RoSMA-18-d 6 is a promising CB2 PET radioligand for clinical translation.

There is a high demand for tumor specific PET tracers in oncology imaging. Besides glucose, certain amino acids also serve as energy sources and anabolic precursors for tumors. Therefore, (18)F-labeled amino acids are interesting probes for tumor specific PET imaging. As glutamine and glutamate play a key role in the adapted intermediary metabolism of tumors, the radiosynthesis of 4-[(18)F]fluoro l-glutamic acid (BAY 85-8050) as a new specific PET tracer was established. Cell-uptake studies revealed specific tumor cell accumulation.