[18F]Fluoropyridines: From Conventional Radiotracers to the Labeling of Macromolecules Such as Proteins and Oligonucleotides

Dollé, Frédéric

doi:10.1007/978-3-540-49527-7_5

Cited by 20 publications

(17 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…31 However, we observe some bone uptake with [ 18 F]- 5 (1.31 ± 0.63 %ID/g) and [ 18 F]- 4a (4.14 ± 1.12 %ID/g) 2h p. i.. In comparison, [ 18 F]-Fluoropentyne based prosthetic group shows very minimal bone uptake (0.39 %ID/g at 1h p.i.).…”

Section: Resultsmentioning

confidence: 64%

“…We chose Fluoropyridinealkyne 3 because of the commercial availability of the corresponding bromo-precursor 6 , its UV-detectability, and the fact that 2-[ 18 F]fluoropyridines were shown to display high in vivo stability. 31 Moreover, the small size of 3 was expected to have a very limited impact on the pharmacokinetic of peptides as large as pHLIP.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Efficient ¹⁸F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

Daumar

Wanger-Baumann²,

Pillarsetty³

et al. 2012

Bioconjugate Chem.

118

View full text Add to dashboard Cite

Solid tumors often develop an acidic microenvironment, which plays a critical role in tumor progression and is associated with increased level of invasion and metastasis. The 37-residue pH (low) insertion peptide (pHLIP®) is under study as an imaging platform because of its unique ability to insert into cell membranes at a low extracellular pH (pHe<7). Labeling of peptides with [18F]-fluorine is usually performed via prosthetic groups using chemoselective coupling reactions. One of the most successful procedures involves the alkyne-azide copper(I) catalyzed cycloaddition (CuAAC). However, none of the known “click” methods have been applied to peptides as large as pHLIP. We designed a novel prosthetic group and extended the use of the CuAAC “click chemistry” for the simple and efficient 18F-labeling of large peptides. For the evaluation of this labeling approach, a D-amino acid analogue of WT-pHLIP and a L-amino acid control peptide K-pHLIP, both functionalized at the N-terminus with 6-azidohexanoic acid, were used. The novel 6-[18F]fluoro-2-ethynylpyridine prosthetic group, was obtained via nucleophilic substitution on the corresponding bromo-precursor after 10 min at 130 °C with a radiochemical yield of 27.5 ± 6.6% (decay corrected) with high radiochemical purity ≥ 98%. The subsequent CuI catalyzed “click” reaction with the azido functionalized pHLIP peptides was quantitative within 5 min at 70 °C in a mixture of water and ethanol using Cu-acetate and sodium L-ascorbate. [18F]-D-WT-pHLIP and [18F]-L-K-pHLIP were obtained with total radiochemical yields of 5–20% after HPLC purification. The total reaction time was only 85 min including formulation. In vitro stability tests revealed high stability of the [18F]-D-WT-pHLIP in human and mouse plasma after 120 min, with the parent tracer remaining intact at 65 and 85%, respectively. PET imaging and biodistribution studies in LNCaP and PC-3 xenografted mice with the [18F]-D-WT-pHLIP and the negative control [18F]-L-K-pHLIP revealed pH-dependent tumor retention. This reliable and efficient protocol promises to be useful for the 18F-labeling of large peptides such as pHLIP and will accelerate the evaluation of numerous [18F]-pHLIP analogues as potential PET tracers.

show abstract

Section: Resultsmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Efficient ¹⁸F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

Daumar

Wanger-Baumann²,

Pillarsetty³

et al. 2012

Bioconjugate Chem.

118

View full text Add to dashboard Cite

show abstract

“…Compared with other radiotracers, the 18 F radiotracer could improve stability and bioavailability of tissue metabolism, enhance the bonding force, and reduce the plasma protein binding rate [44]. Incorporating 18 F into a compound alters the lipophilic parameter and might increase the intrinsic activity, metabolic stability, and bioavailability [45].…”

Section: Mitochondrial-targeted Pet Agentsmentioning

confidence: 99%

Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

Lu²,

Zhou

2017

BioMed Research International

View full text Add to dashboard Cite

The present study aimed to discuss the role of mitochondrion in cardiac function and disease. The mitochondrion plays a fundamental role in cellular processes ranging from metabolism to apoptosis. The mitochondrial-targeted molecular imaging could potentially illustrate changes in global and regional cardiac dysfunction. The collective changes that occur in mitochondrial-targeted molecular imaging probes have been widely explored and developed. As probes currently used in the preclinical setting still have a lot of shortcomings, the development of myocardial metabolic activity, viability, perfusion, and blood flow molecular imaging probes holds great potential for accurately evaluating the myocardial viability and functional reserve. The advantages of molecular imaging provide a perspective on investigating the mitochondrial function of the myocardium in vivo noninvasively and quantitatively. The molecular imaging tracers of single-photon emission computed tomography and positron emission tomography could give more detailed information on myocardial metabolism and restoration. In this study, series mitochondrial-targeted 99mTc-, 123I-, and 18F-labeled tracers displayed broad applications because they could provide a direct link between mitochondrial dysfunction and cardiac disease.

show abstract

“…18 F labeled siRNA analogs for PET imaging). Fluorine-18 labeled oligonucleotides have been already tested as labeled imaging probes in vivo (Boisgard et al, 2005; Dolle, 2007). With the development of more quantitative in vivo imaging experiments the current animal studies involving siRNA could be either complemented with, or replaced entirely by survival (and longitudinal) imaging studies.…”

Section: Assessment Of Rnai Delivery Using Imagingmentioning

confidence: 99%

Merging molecular imaging and RNA interference: Early experience in live animals

Bogdanov

2008

J of Cellular Biochemistry

View full text Add to dashboard Cite

The rapid development of non-invasive imaging techniques and imaging reporters coincided with the enthusiastic response that the introduction of RNAi (RNA interference) techniques created in the research community. Imaging in experimental animals provides quantitative or semi-quantitative information regarding the biodistribution of small interfering RNAs and the levels of gene interference (i.e. knockdown of the target mRNA) in living animals. In this review we give a brief summary of the first imaging findings that have potential for accelerating the development and testing of new approaches that explore RNAi as a method for achieving loss-of-function effects in vivo and as a promising therapeutic tool.

show abstract

[18F]Fluoropyridines: From Conventional Radiotracers to the Labeling of Macromolecules Such as Proteins and Oligonucleotides

Cited by 20 publications

References 109 publications

Efficient ¹⁸F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

Efficient ¹⁸F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

Merging molecular imaging and RNA interference: Early experience in live animals

Contact Info

Product

Resources

About

[18F]Fluoropyridines: From Conventional Radiotracers to the Labeling of Macromolecules Such as Proteins and Oligonucleotides

Cited by 20 publications

References 109 publications

Efficient 18F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

Efficient 18F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

Merging molecular imaging and RNA interference: Early experience in live animals

Contact Info

Product

Resources

About

Efficient ¹⁸F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation

Efficient ¹⁸F-Labeling of Large 37-Amino-Acid pHLIP Peptide Analogues and Their Biological Evaluation