A facile automated synthesis of N‐succinimidyl 4‐[18F]fluorobenzoate ([18F]SFB) for 18F‐labeled cell‐penetrating peptide as PET tracer

Tang, Ganghua; Tang, Xiaolan; Wang, Xinlu

doi:10.1002/jlcr.1758

Cited by 49 publications

(33 citation statements)

References 14 publications

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“…Dried 18 F-SFB was produced using a 3-step 1-pot procedure as previously described (17,18). FVIIai (1.0 mg in 400 mL of N-(2-hydroxyethyl)piperazine-N-(2-ethanesulfonic acid) buffer, pH 7.5) was added to the dried 18 F-SFB and stirred for 1 h at room temperature to yield 18 F-FVIIai.…”

Section: Radiochemistrymentioning

confidence: 99%

Quantitative PET Imaging of Tissue Factor Expression Using ¹⁸F-Labeled Active Site–Inhibited Factor VII

et al. 2015

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Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an 18 F-labeled derivative of factor VII. Methods: Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-18 F-fluorobenzoate and purified. The corresponding product, 18 F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of 18 F-FVIIai in the tumors measured in vivo by PET imaging. Results: The PET images showed high uptake of 18 F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of 18 F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of 18 F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P , 0.001). The uptake of 18 F-FVIIai measured in vivo by PET imaging correlated (r 5 0.72, P , 0.02) with TF protein level measured ex vivo. Conclusion: 18 F-FVIIai is a promising PET tracer for specific and noninvasive imaging of tumor TF expression. The tracer merits further development and clinical translation, with potential to become a companion diagnostics for emerging TF-targeted therapies.

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Section: Radiochemistrymentioning

confidence: 99%

Quantitative PET Imaging of Tissue Factor Expression Using ¹⁸F-Labeled Active Site–Inhibited Factor VII

et al. 2015

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“…N ‐Succinimidyl 4‐[ 18 F]fluorobenzoate was used as a prosthetic group to label ASIS with 18 F, as it conjugates to amino groups at physiological pH and is therefore suitable for labeling the available lysine residues or the amino terminals present in ASIS …”

Section: Resultsmentioning

confidence: 99%

“…N ‐Succinimidyl 4‐[ 18 F]fluorobenzoate ([ 18 F]SFB) was synthesized on an automated radiochemistry module using a three‐step, one‐pot procedure modified from that of Tang et al . [ 18 F]Fluoride was transferred from the cyclotron target with helium gas and trapped on a QMA cartridge.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and characterization of ¹⁸F‐labeled active site inhibited factor VII (ASIS)

Erlandsson

Nielsen

Jeppesen

et al. 2015

Labelled Comp Radiopharmac

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Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress.

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“…Among the amine reactive prosthetic groups [12, 27–36], N-succinimidyl 4-[ 18 F]fluorobenzoate ([ 18 F]SFB) [12, 31–36] is the most extensively studied and several modifications have been made to improve the synthesis procedure since it was first reported [31] by Vaidyanathan et al in 1992. However, the preparation of [ 18 F]SFB is a time consuming multi-step synthesis procedure that includes an HPLC purification step.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging

Basuli¹,

Li²,

Xu³

et al. 2015

Nuclear Medicine and Biology

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We sought to develop a practical, reproducible and clinically translatable method of radiolabeling serum albumins with fluorine-18 for use as a PET blood pool imaging agent in animals and man. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [18F]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [18F]tetrabutylammonium fluoride ([18F]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [18F]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH 9) for 15 min at 37–40 °C produced fluorine-18-radiolabeled RSA and the product was purified using a mini-PD MiniTrap G-25 column. The overall radiochemical yield of the reaction was 18–35% (n = 30, uncorrected) in a 90-min synthesis. This procedure, repeated with human serum albumin (HSA), yielded similar results. Fluorine-18-radiolabeled RSA demonstrated prolonged blood retention (biological half-life of 4.8 hours) in healthy awake rats. The distribution of major organ radioactivity remained relatively unchanged during the 4 hour observation periods either by direct tissue counting or by dynamic PET whole-body imaging except for a gradual accumulation of labeled metabolic products in the bladder. This manual method for synthesizing radiolabeled serum albumins uses fluorine-18, a widely available PET radionuclide, and natural protein available in both pure and recombinant forms which could be scaled up for widespread clinical applications. These preclinical biodistribution and PET imaging results indicate that [18F]RSA is an effective blood pool imaging agent in rats and might, as [18F]HSA, prove similarly useful as a clinical imaging agent.

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A facile automated synthesis of N‐succinimidyl 4‐[¹⁸F]fluorobenzoate ([¹⁸F]SFB) for ¹⁸F‐labeled cell‐penetrating peptide as PET tracer

Cited by 49 publications

References 14 publications

Quantitative PET Imaging of Tissue Factor Expression Using ¹⁸F-Labeled Active Site–Inhibited Factor VII

Quantitative PET Imaging of Tissue Factor Expression Using ¹⁸F-Labeled Active Site–Inhibited Factor VII

Synthesis and characterization of ¹⁸F‐labeled active site inhibited factor VII (ASIS)

Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging

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A facile automated synthesis of N‐succinimidyl 4‐[18F]fluorobenzoate ([18F]SFB) for 18F‐labeled cell‐penetrating peptide as PET tracer

Cited by 49 publications

References 14 publications

Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site–Inhibited Factor VII

Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site–Inhibited Factor VII

Synthesis and characterization of 18F‐labeled active site inhibited factor VII (ASIS)

Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging

Contact Info

Product

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A facile automated synthesis of N‐succinimidyl 4‐[¹⁸F]fluorobenzoate ([¹⁸F]SFB) for ¹⁸F‐labeled cell‐penetrating peptide as PET tracer

Quantitative PET Imaging of Tissue Factor Expression Using ¹⁸F-Labeled Active Site–Inhibited Factor VII

Quantitative PET Imaging of Tissue Factor Expression Using ¹⁸F-Labeled Active Site–Inhibited Factor VII

Synthesis and characterization of ¹⁸F‐labeled active site inhibited factor VII (ASIS)