Optimal 18F-fluorination conditions for the high radiochemical yield of [18F]AlF-NOTA-NHS complexes

18F-fluorination using aluminum-fluoride ([18F]AlF) chelate technique has been reported to give a low-to-moderate radiochemical yield, between 5 and 20%. Therefore, the work described here outlines the optimum 18F-fluorination condition for the formation of [18F]AlF2+ and [18F]AlF-NOTA-NHS complex with the radiochemical yield (RCY) and purity (RCP) of more than 90% as a prerequisite step before proceeding with the radiopharmaceutical preparation using the [18F]AlF-bifunctional chelator technique. As well as being simple, the suggested method is practical and relevant for beginners interested in 18F-fluorination with [18F]AlF-chelate complex technique or also for a researcher who aims to proceed on an extensive scale.

Immuno-PET Molecular Imaging of RANKL in Cancer

Purpose: The involvement of RANK/RANKL signaling in the tumor microenvironment (TME) in driving response or resistance to immunotherapy has only very recently been recognized. Current quantification methods of RANKL expression suffer from issues such as sensitivity, variability, and uncertainty on the spatial heterogeneity within the TME, resulting in conflicting reports on its reliability and limited use in clinical practice. Non-invasive molecular imaging using immuno-PET is a promising approach combining superior targeting specificity of monoclonal antibodies (mAb) and spatial, temporal and functional information of PET. Here, we evaluated radiolabeled anti-RANKL mAbs as a non-invasive biomarker of RANKL expression in the TME. Experimental design: Anti-human RANKL mAbs (AMG161 and AMG162) were radiolabeled with 89Zr using the bifunctional chelator DFO in high yield, purity and with intact binding affinity. After assessing the biodistribution in healthy CD-1 nude mice, [89Zr]Zr-DFO-AMG162 was selected for further evaluation in ME-180 (RANKL-transduced), UM-SCC-22B (RANKL-positive) and HCT-116 (RANKL-negative) human cancer xenografts to assess the feasibility of in vivo immuno-PET imaging of RANKL. Results: [89Zr]Zr-DFO-AMG162 was selected as the most promising tracer for further validation based on biodistribution experiments. We demonstrated specific accumulation of [89Zr]Zr-DFO-AMG162 in RANKL transduced ME-180 xenografts. In UM-SCC-22B xenograft models expressing physiological RANKL levels, [89Zr]Zr-DFO-AMG162 imaging detected significantly higher signal compared to control [89Zr]Zr-DFO-IgG2 and to RANKL negative HCT-116 xenografts. There was good visual agreement with tumor autoradiography and immunohistochemistry on adjacent slides, confirming these findings. Conclusions: [89Zr]Zr-DFO-AMG162 can detect heterogeneous RANKL expression in the TME of human cancer xenografts, supporting further translation of RANKL immuno-PET to evaluate tumor RANKL distribution in patients.

Design of a multivalent bifunctional chelator for diagnostic64Cu PET imaging in Alzheimer’s disease

Herein, we report a64Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable blood–brain barrier penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding64Cu PET imaging agent.

Successful Design of a Multivalent Bifunctional Chelator for Diagnostic 64Cu PET Imaging in Alzheimer’s Disease

Herein, we report to the best of our knowledge the first ⁶⁴Cu PET imaging agent that shows appreciable <i>in vivo</i> brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of WT mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable BBB penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the <i>in vivo</i> Aβ-binding specificity and brain uptake of the corresponding ⁶⁴Cu PET imaging agent.

Successful Design of a Multivalent Bifunctional Chelator for Diagnostic 64Cu PET Imaging in Alzheimer’s Disease

Herein, we report to the best of our knowledge the first ⁶⁴Cu PET imaging agent that shows appreciable <i>in vivo</i> brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of WT mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable BBB penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the <i>in vivo</i> Aβ-binding specificity and brain uptake of the corresponding ⁶⁴Cu PET imaging agent.

Chelation with a twist: a bifunctional chelator to enable room temperature radiolabeling and targeted PET imaging with scandium-44

The small-cavity, bifunctional chelator picaga coordinates Sc-44 at room temperature and enables PET imaging of an in vivo tumor target.