The aluminium-[18F]fluoride ([18F]AlF) radiolabelling method combines the favourable decay characteristics of fluorine-18 with the convenience and familiarity of metal-based radiochemistry and has been used to parallel gallium-68 radiopharmaceutical developments. As such, the [18F]AlF method is popular and widely implemented in the development of radiopharmaceuticals for the clinic. In this review, we capture the current status of [18F]AlF-based technology and reflect upon its impact on nuclear medicine, as well as offering our perspective on what the future holds for this unique radiolabelling method.

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Expression of the chemokine receptor chemokine C-X-C motif receptor 4 (CXCR4) plays an important role in cancer metastasis, in autoimmune diseases, and during stem cell-based repair processes after stroke and myocardial infarction. Previously reported PET imaging agents targeting CXCR4 suffer from either high nonspecific uptake or bind only to the human form of the receptor. The objective of this study was to develop a high-stability 64 Cu-labeled smallmolecule PET agent for imaging both human and murine CXCR4 chemokine receptors. Methods: Synthesis, radiochemistry, stability and radioligand binding assays were performed for the novel tracer 64 Cu-CuCB-bicyclam. In vivo dynamic PET studies were performed on mice bearing U87 (CXCR4 low-expressing) and U87.CXCR4 (human-CXCR4 high-expressing) tumors. Biodistribution and receptor blocking studies were performed on CD1-IGS immunocompetent mice. CXCR4 expression on tumor and liver disaggregates was confirmed using a combination of immunohistochemistry, quantitative polymerase chain reaction, and Western blot. Results: 64 Cu-CuCB-bicyclam has a high affinity for both the human and the murine variants of the CXCR4 receptor (half-maximal inhibitory concentration, 8 nM [human]/2 nM [murine]) and can be obtained from the parent chelator that has low affinity. In vitro and in vivo studies demonstrate specific uptake in CXCR4-expressing cells that can be blocked by more than 90% using a higher-affinity antagonist, with limited uptake in non-CXCR4-expressing organs and high in vivo stability. The tracer was also able to selectively displace the CXCR4 antagonists AMD3100 and AMD3465 from the liver. Conclusion: The tetraazamacrocyclic small molecule 64 Cu-CuCB-bicyclam has been shown to be an imaging agent for the CXCR4 receptor that is likely to be applicable across a range of species. It has high affinity and stability and is suitable for preclinical research in immunocompetent murine models.

Introduction Time-of-flight (TOF) positron emission tomography (PET) scanners can provide significant benefits by improving the noise properties of reconstructed images. In order to achieve this, the timing response of the scanner needs to be modelled as part of the reconstruction process. This is currently achieved using Gaussian TOF kernels. However, the timing measurements do not necessarily follow a Gaussian distribution. In ultra-fast timing resolutions, the depth of interaction of the γ-photon and the photon travel spread (PTS) in the crystal volume become increasingly significant factors for the timing performance. The PTS of a single photon can be approximated better by a truncated exponential distribution. Therefore, we computed the corresponding TOF kernel as a modified Laplace distribution for long crystals. The obtained (CTR) kernels could be more appropriate to model the joint probability of the two in-coincidenceγ-photons. In this paper, we investigate the impact of using a CTR kernel vs. Gaussian kernels in TOF reconstruction using Monte Carlo generated data. Materials and methods The geometry and physics of a PET scanner with two timing configurations, (a) idealised timing resolution, in which only the PTS contributed in the CTR, and (b) with a range of ultra-fast timings, were simulated. In order to assess the role of the crystal thickness, different crystal lengths were considered. The evaluation took place in terms of Kullback–Leibler (K-L) distance between the proposed model and the simulated timing response, contrast recovery (CRC) and spatial resolution. The reconstructions were performed using STIR image reconstruction toolbox. Results Results for the idealised scanner showed that the CTR kernel was in excellent agreement with the simulated time differences. In terms of K-L distance outperformed the a fitted normal distribution for all tested crystal sizes. In the case of the ultra-fast configurations, a convolution kernel between the CTR and a Gaussian showed the best agreement with the simulated data below 40 ps timing resolution. In terms of CRC, the CTR kernel demonstrated improvements, with values that ranged up to 3.8% better CRC for the thickest crystal. In terms of spatial resolution, evaluated at the 60th iteration, the use of CTR kernel showed a modest improvement of the peek-to-valley ratios up to 1% for the 10-mm crystal, while for larger crystals, a clear trend was not observed. In addition, we showed that edge artefacts can appear in the reconstructed images when the timing kernel used for the reconstruction is not carefully optimised. Further iterations, can help improve the edge artefacts.