Bridging the gaps in 18F PET tracer development

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.

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PET tracer development - a tale of mice and men

Cancer Imaging ◽

10.1102/1470-7330.2006.9098 ◽

2006 ◽

Vol 6 (Special Issue A) ◽

pp. S102-S106 ◽

Cited By ~ 10

Author(s):

Rodney J. Hicks

Keyword(s):

Pet Tracer ◽

Of Mice And Men ◽

Tracer Development

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

Chemical Communications ◽

10.1039/c8cc10166c ◽

2019 ◽

Vol 55 (25) ◽

pp. 3630-3633 ◽

Cited By ~ 4

Author(s):

Jian Yang ◽

Ran Cheng ◽

Hualong Fu ◽

Jing Yang ◽

Mohanraja Kumar ◽

...

Keyword(s):

Amyloid Beta ◽

Pet Imaging ◽

Curcumin Analogues ◽

Pet Tracer ◽

Beta Species ◽

Imaging Probes ◽

Tracer Development

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

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Modular Approaches in PET-tracer Development: Radiotracer Design, Synthesis and Automation for Prostate Cancer and Heart Failure

10.33612/diss.133809999 ◽

2020 ◽

Author(s):

◽

Verena Böhmer

Keyword(s):

Prostate Cancer ◽

Heart Failure ◽

Design Synthesis ◽

Pet Tracer ◽

Tracer Development

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

10.26434/chemrxiv.14229491.v1 ◽

2021 ◽

Author(s):

Klas Bratteby ◽

Vladimir Shalgunov ◽

Umberto Maria Battisti ◽

Ida Nymann Petersen ◽

Sara Lopes van den Broek ◽

...

Keyword(s):

Anion Exchange ◽

Reaction Medium ◽

Radiochemical Yield ◽

Emission Tomography ◽

Pet Tracers ◽

High Basicity ◽

Pet Tracer ◽

Positron Emission ◽

Polar Reaction ◽

Tracer Development

Aliphatic nucleophilic substitution (SN2) 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 SN2 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 SN2 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 SN2 18F-fluorination of base-sensitive substrates.

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

10.26434/chemrxiv.14229491 ◽

2021 ◽

Author(s):

Klas Bratteby ◽

Vladimir Shalgunov ◽

Umberto Maria Battisti ◽

Ida Nymann Petersen ◽

Sara Lopes van den Broek ◽

...

Keyword(s):

Anion Exchange ◽

Reaction Medium ◽

Radiochemical Yield ◽

Emission Tomography ◽

Pet Tracers ◽

High Basicity ◽

Pet Tracer ◽

Positron Emission ◽

Polar Reaction ◽

Tracer Development

Aliphatic nucleophilic substitution (SN2) 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 SN2 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 SN2 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 SN2 18F-fluorination of base-sensitive substrates.

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Detecting oxytocin: mass spectrometry and PET-tracer development

10.14264/1d1bf43 ◽

2020 ◽

Author(s):

◽

Anke Hering

Keyword(s):

Mass Spectrometry ◽

Pet Tracer ◽

Tracer Development

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Dopamine D1 Receptor Agonist PET Tracer Development: Assessment in Non-Human Primates

Journal of Nuclear Medicine ◽

10.2967/jnumed.120.256008 ◽

2021 ◽

pp. jnumed.120.256008

Author(s):

Olivier Barret ◽

Lei Zhang ◽

David Alagille ◽

Cristian C. Constantinescu ◽

Christine Sandiego ◽

...

Keyword(s):

Receptor Agonist ◽

Dopamine D1 Receptor ◽

D1 Receptor ◽

Pet Tracer ◽

Development Assessment ◽

Tracer Development

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Comparison of diagnostic accuracy of 18F-FDG PET, 123I-IMT- and 99mTc-MIBI SPECT

Nuklearmedizin ◽

10.1055/s-0038-1623934 ◽

2006 ◽

Vol 45 (01) ◽

pp. 49-56 ◽

Cited By ~ 2

Author(s):

N. Özdemir-Sahin ◽

P. Hipp ◽

W. Mier ◽

M. Eisenhut ◽

J. Debus ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Fdg Pet ◽

Tumour Progression ◽

Roc Curves ◽

Low Grade ◽

Who Grade ◽

Pet Tracer ◽

Patient Groups ◽

99Mtc Mibi ◽

Mibi Spect

Summary Aim was to evaluates the diagnostic accuracy of the SPECTtracers 3-123I-α-methyl-L-tyrosine (IMT) and 99mTc(I)- hexakis(2-methoxyisobutylisonitrile) (MIBI) as well as the PET-tracer 2-18F-2-deoxyglucose (FDG) for detecting tumour progression in irradiated low grade astrocytomas (LGA). Patients, methods: We examined 91 patients (56 males; 35 females; 44.7 ± 11.5 years), initially suffering from histologically proven LGAs (mean WHO grade II) and treated by stereotactic radiotherapy (59.0 ± 4.6 Gy). On average 21.9 ± 11.2 months after radiotherapy, patients presented new Gd-DTPA enhancing lesions on MRI, which did not allow a differentiation between progressive tumour (PT) and non-PT (nPT) at this point of time. PET scans (n=82) were acquired 45 min after injection of 208 ± 32 MBq FDG. SPECT scans started 10 min after injection of 269 ± 73 MBq IMT (n=68) and 15 min after injection of 706 ± 63 MBq MIBI (n=34). Lesions were classified as PT and nPT based on prospective follow-up (clinically, MRI) for 17.2 ± 9.9 months after PET/SPECT. Lesion-to-normal ratios (L/N) were calculated using contra lateraly mirrored reference regions for the SPECT examinations and reference regions in the contra lateral grey (GM) and white matter (WM) for FDG PET. Ratios were evaluated by Receiver Operating Characteristic (ROC) analysis. Results: In the patient groups nPT and PT, L/N ratios for FDG (GS) were 0.6 ± 0.3 vs. 1.2 ± 0.5 (p = 0.003), for FDG (WS) 1.2 ± 0.4 vs. 2.6 ± 0.4 (p <0.001), for IMT 1.1 ± 0.1 vs. 1.8 ± 0.4 (p <0.001) and for MIBI 1.6 ± 0.7 vs. 2.6 ± 2.2 (p = 0.554). Areas under the non-parametric ROC-curves were: 0.738 ± 0.059 for FDG (GS), 0.790 ± 0.057 for FDG (WS), 0.937 ± 0.037 for IMT and 0.564 ± 0.105 for MIBI. Conclusion: MIBI-SPECT examinations resulted in a low accuracy and especially in a poor sensitivity even at modest specificity values. A satisfying diagnostic accuracy was reached with FDG PET. Using WM as reference region for FDG PET, a slightly higher AUC as compared to GM was calculated. IMT yielded the best ROC characteristics and the highest diagnostic accuracy for differentiating between PT and nPT in irradiated LGA.

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