Magnetic particle imaging: tracer development and the biomedical applications of a radiation-free, sensitive, and quantitative imaging modality

Magnetic particle imaging (MPI) is an emerging tracer-based modality that enables real-time three-dimensional imaging of the non-linear magnetisation produced by superparamagnetic iron oxide nanoparticles (SPIONs), in the presence of an...

Update on PET Tracer Development for Muscarinic Acetylcholine Receptors

The muscarinic cholinergic system regulates peripheral and central nervous system functions, and, thus, their potential as a therapeutic target for several neurodegenerative diseases is undoubted. A clinically applicable positron emission tomography (PET) tracer would facilitate the monitoring of disease progression, elucidate the role of muscarinic acetylcholine receptors (mAChR) in disease development and would aid to clarify the diverse natural functions of mAChR regulation throughout the nervous system, which still are largely unresolved. Still, no mAChR PET tracer has yet found broad clinical application, which demands mAChR tracers with improved imaging properties. This paper reviews strategies of mAChR PET tracer design and summarizes the binding properties and preclinical evaluation of recent mAChR tracer candidates. Furthermore, this work identifies the current major challenges in mAChR PET tracer development and provides a perspective on future developments in this area of research.

Insights into Elution of Anion Exchange Cartridges: Opening the Path towards Aliphatic 18F-Radiolabeling of Base-Sensitive Tracers

Aliphatic nucleophilic substitution (S_N2) with [¹⁸F]fluoride is the most widely applied method to prepare ¹⁸F-labeled positron emission tomography (PET) tracers. Strongly basic conditions commonly used during ¹⁸F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The high basicity stems from the tradition to trap [¹⁸F]fluoride on anion exchange cartridges and elute it afterwards with basic anions. This sequence is used to facilitate the transfer of [¹⁸F]fluoride from an aqueous to an aprotic organic, polar reaction medium, which is beneficial for S_N2 reactions. Furthermore, this sequence also removes cationic radioactive contaminations from cyclotron-irradiated [¹⁸O]water from which [¹⁸F]fluoride is produced. In this study, we developed an efficient elution procedure resulting in low basicity that permits S_N2 ¹⁸F-labeling of base-sensitive scaffolds. Extensive screening of trapping and elution conditions (>1000 experiments) and studying their influence on the radiochemical yield (RCY) allowed us to identify a suitable procedure for this. Four PET tracers and three synthons could be radiolabeled in substantially higher RCYs (up to 2.5-fold), even from lower precursor amounts, using this procedure. Encouraged by these results, we applied our low basicity method to the radiolabeling of highly base-sensitive tetrazines, which cannot be labeled using state-of-art direct aliphatic ¹⁸F-labeling procedures. Labeling succeeded in RCYs of up to 20%. We believe that our findings facilitate PET tracer development by opening the path towards simple and direct S_N2 ¹⁸F-fluorination of base-sensitive substrates.

Insights into Elution of Anion Exchange Cartridges: Opening the Path towards Aliphatic 18F-Radiolabeling of Base-Sensitive Tracers

Aliphatic nucleophilic substitution (S_N2) with [¹⁸F]fluoride is the most widely applied method to prepare ¹⁸F-labeled positron emission tomography (PET) tracers. Strongly basic conditions commonly used during ¹⁸F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The high basicity stems from the tradition to trap [¹⁸F]fluoride on anion exchange cartridges and elute it afterwards with basic anions. This sequence is used to facilitate the transfer of [¹⁸F]fluoride from an aqueous to an aprotic organic, polar reaction medium, which is beneficial for S_N2 reactions. Furthermore, this sequence also removes cationic radioactive contaminations from cyclotron-irradiated [¹⁸O]water from which [¹⁸F]fluoride is produced. In this study, we developed an efficient elution procedure resulting in low basicity that permits S_N2 ¹⁸F-labeling of base-sensitive scaffolds. Extensive screening of trapping and elution conditions (>1000 experiments) and studying their influence on the radiochemical yield (RCY) allowed us to identify a suitable procedure for this. Four PET tracers and three synthons could be radiolabeled in substantially higher RCYs (up to 2.5-fold), even from lower precursor amounts, using this procedure. Encouraged by these results, we applied our low basicity method to the radiolabeling of highly base-sensitive tetrazines, which cannot be labeled using state-of-art direct aliphatic ¹⁸F-labeling procedures. Labeling succeeded in RCYs of up to 20%. We believe that our findings facilitate PET tracer development by opening the path towards simple and direct S_N2 ¹⁸F-fluorination of base-sensitive substrates.

Half-curcumin analogues as PET imaging probes for amyloid beta species

In this report, we demonstrate that half-curcuminoid could be a better scaffold for PET tracer development.