PET Designated Flouride-18 Production and Chemistry

Jacobson, Orit; Chen, Xiaoyuan

doi:10.2174/156802610791384298

Cited by 51 publications

(42 citation statements)

References 91 publications

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“…Organic prosthetic groups (Figure 2: 4-FB, 4-FBz, 2-FP and 2-FDG) are needed for 18 F-labeling. 76–89 Because of aromatic rings, 4-FB, 4-FBz and 2-FP groups often have relatively high lipophilicity, which might lead to more hepatobiliary excretion. The results from recent studies indicate that Al(NOTA) (Figure 2) is highly efficient for routine radiosynthesis of 18 F-labeled small biomolecule radiotracers using the kit formulation.…”

Section: Radiotracer Designmentioning

confidence: 99%

Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins

Liu

2015

Bioconjugate Chem.

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Angiogenesis is a requirement for tumor growth and metastasis. The angiogenic process depends on vascular endothelial cell migration and invasion, and is regulated by various cell adhesion receptors. Integrins are such a family of receptors that facilitate the cellular adhesion to and migration on extracellular matrix proteins in the intercellular spaces and basement membranes. Among 24 members of the integrin family, αvβ3 is studied most extensively for its role in tumor angiogenesis and metastasis. The αvβ3 is expressed at relatively low levels on epithelial cells and mature endothelial cells, but it is highly expressed on the activated endothelial cells of tumor neovasculature and some tumor cells. This restricted expression makes αvβ3 an excellent target to develop antiangiogenic drugs and diagnostic molecular imaging probes. Since αvβ3 is a receptor for extracellular matrix proteins with one or more RGD tripeptide sequence, many radiolabeled cyclic RGD peptides have been evaluated as “αvβ3–targeted” radiotracers for tumor imaging over the last decade. This article will use the dimeric and tetrameric cyclic RGD peptides developed in our laboratories as examples to illustrate basic principles for development of αvβ3–targeted radiotracers. It will focus on different approaches to maximize the radiotracer tumor uptake and tumor/background ratios. This article will also discuss some important assays for pre-clinical evaluations of integrin–targeted radiotracers. In general, multimerization of cyclic RGD peptides increases their integrin binding affinity and the tumor uptake and retention times of their radiotracers. Regardless of their multiplicity, the capability of cyclic RGD peptides to bind other integrins (namely αvβ5, α5β1, α6β4, α4β1 and αvβ6) is expected to enhance the radiotracer tumor uptake due to the increased integrin population. The result from preclinical and clinical studies clearly show that radiolabeled cyclic RGD peptides (such as 99mTc-3P-RGD2, 18F-Alfatide-I and 18F-Alfatide-II) are useful as the molecular imaging probes for early cancer detection and noninvasive monitoring of the tumor response to antiangiogenic therapy.

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Section: Radiotracer Designmentioning

confidence: 99%

Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins

Liu

2015

Bioconjugate Chem.

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“…Fluorine-18 has preferable properties for clinical purposes mainly because of its suitable half-life (109.8 min) and its high positron efficiency (97 %) [29]; therefore, in this study, we report on a simple and rapid F-18 labeling of T140 derivative, Al[ 18 F]NOTA-T140 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Al[18F]NOTA-T140 Peptide for Noninvasive Visualization of CXCR4 Expression

et al. 2015

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Purpose Chemokine receptor CXCR4 plays an important role in tumor aggressiveness, invasiveness, and metastasis formation. Quantification of CXCR4 expression by tumors may have an impact on prediction and evaluation of tumor response to therapies. In this study, we developed a robust and straightforward F-18 labeling route of T140, a CXCR4 peptide-based antagonist. Procedures T140 derivative was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and labeled with Al[18F]. Al[18F]NOTA-T140 was evaluated in vitro in cell-based assay and stability in mouse serum and in vivo using CXCR4 positive and negative tumor xenograft models. Results Labeling of Al[18F]NOTA-T140 was completed within 30 min with a radiochemical yield of 58±5.3 % at the end of synthesis, based on fluoride-18 activity. Al[18F]NOTA-T140 accumulated in CHO-CXCR4 positive but not negative tumors. Al[18F]NOTA-T140 uptake in the tumors correlated with CXCR4 protein expression. Moreover, Al[18F]NOTA-T140 had high accumulation in CXCR4-positive metastatic tumors. Conclusions The simplicity of Al[18F]NOTA-T140 labeling along with its properties to specifically image CXCR4 expression by tumors warrant further clinical application for the diagnosis of CXCR4 clinically.

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“…Recently, major advances have been made in simplifying 18 F-labeled bioactive molecules [21]–[24]. The fluorophilic nature of aluminum is most attractive since it affords direct aqueous 18 F-labeling by the formation of stable aluminum fluoride chelates.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Analysis and Comparison Study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 Using a Reference Tissue Model

Guo

Lang

et al. 2012

PLoS ONE

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With favorable pharmacokinetics and binding affinity for αvβ3 integrin, 18F-labeled dimeric cyclic RGD peptide ([18F]FPPRGD2) has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an 18F-fluoride-aluminum complex labeled RGD tracer ([18F]AlF-NOTA-PRGD2), provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare 68Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin αvβ3. The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [18F]FPPRGD2, [18F]AlF-NOTA-PRGD2, and [68Ga]Ga-NOTA-PRGD2. U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the injection of three tracers. Kinetic parameters were calculated using Logan graphical analysis with reference tissue. Parametric maps were generated using voxel-level modeling. All three compounds showed high binding potential (BpND = k3/k4) in tumor voxels. [18F]AlF-NOTA-PRGD2 showed comparable BpND value (3.75±0.65) with those of [18F]FPPRGD2 (3.39±0.84) and [68Ga]Ga-NOTA-PRGD2 (3.09±0.21) (p>0.05). Little difference was found in volume of distribution (VT) among these three RGD tracers in tumor, liver and muscle. Parametric maps showed similar kinetic parameters for all three tracers. We also demonstrated that the impact of non-specific binding could be eliminated in the kinetic analysis. Consequently, kinetic parameter estimation showed more comparable results among groups than static image analysis. In conclusion, [18F]AlF-NOTA-PRGD2 and [68Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [18F]FPPRGD2. Despite the apparent difference in tumor uptake (%ID/g determined from static images) and clearance pattern, the actual specific binding component extrapolated from kinetic modeling appears to be comparable for all three dimeric RGD tracers.

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PET Designated Flouride-18 Production and Chemistry

Cited by 51 publications

References 91 publications

Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins

Radiolabeled Cyclic RGD Peptide Bioconjugates as Radiotracers Targeting Multiple Integrins

Al[18F]NOTA-T140 Peptide for Noninvasive Visualization of CXCR4 Expression

Quantitative Analysis and Comparison Study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 Using a Reference Tissue Model

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