Dataset Information

Fully automated ¹⁸F-fluorination of N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) for indirect labelling of nanobodies.

ABSTRACT: N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB), a widely used labeling agent to introduce the 4-[¹⁸F]fluorobenzoyl-prosthetic group, is normally obtained in three consecutive steps from [¹⁸F]fluoride ion. Here, we describe an efficient one-step labeling procedure of [¹⁸F]SFB starting from a tin precursor. This method circumvents volatile radioactive side-products and simplifies automatization. [¹⁸F]SFB was obtained after HPLC purification in a yield of 42 + 4% and a radiochemical purity (RCP) > 99% (n = 6). In addition, we investigate the automation of the coupling of [¹⁸F]SFB to a nanobody (cAbBcII10, targeting β-lactamase enzyme) and purification by size exclusion chromatography (PD-10 desalting column) to remove unconjugated reagent. Production and use of [¹⁸F]SFB were implemented on a radiosynthesis unit (Neptis^®). The fully automated radiosynthesis process including purification and formulation required 160 min of synthesis time. [¹⁸F]SFB-labeled nanobody was obtained in a yield of 21 + 2% (activity yield 12 + 1% non-decay corrected) and a radiochemical purity (RCP) of > 95% (n = 3). This approach simplifies [¹⁸F]SFB synthesis to one-step, enhances the yield in comparison to the previous report and enables the production of radiolabeled nanobody on the same synthesis module.

SUBMITTER: Nagachinta S

PROVIDER: S-EPMC9636270 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Fully automated 18F-fluorination of N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) for indirect labelling of nanobodies.

Nagachinta Surasa S Novelli Paolo P Joyard Yoann Y Maindron Nicolas N Riss Patrick P Dammicco Sylvestre S

Scientific reports 20221104 1

N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB), a widely used labeling agent to introduce the 4-[18F]fluorobenzoyl-prosthetic group, is normally obtained in three consecutive steps from [18F]fluoride ion. Here, we describe an efficient one-step labeling procedure of [18F]SFB starting from a tin precursor. This method circumvents volatile radioactive side-products and simplifies automatization. [18F]SFB was obtained after HPLC pur ...[more]

PMID: 36333403

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Project description:Integrin ?v?6 is a cell surface receptor minimally expressed by healthy tissue but elevated in lung, colon, skin, ovarian, cervical, and pancreatic cancers. A molecular PET agent for integrin ?v?6 could provide significant clinical utility by facilitating both cancer staging and treatment monitoring to more rapidly identify an effective therapeutic approach.Here, we evaluated 2 cystine knot peptides, R01 and S02, previously engineered with a 3-6 nM affinity for integrin ?v?6, for (18)F radiolabeling and PET imaging of BxPC3 pancreatic adenocarcinoma xenografts in mice. Cystine knot peptides were labeled with N-succinimidyl-4-(18)F-fluorobenzoate and evaluated for binding affinity and serum stability. Peptides conjugated with (18)F-fluorobenzoate (2-3 MBq) were injected via the tail vein into nude mice xenografted with BxPC3 (integrin ?v?6-positive) or 293 (integrin ?v?6-negative) tumors. Small-animal PET scans were acquired at 0.5, 1, and 2 h after injection. Ex vivo ?-counting of dissected tissues was performed at 0.5 and 2 h.(18)F-fluorobenzoate peptides were produced in 93% ((18)F-fluorobenzoate-R01) and 99% ((18)F-fluorobenzoate-S02) purity. (18)F-fluorobenzoate-R01 and (18)F-fluorobenzoate-S02 had affinities of 1.1 ± 0.2 and 0.7 ± 0.4 nM, respectively, and were 87% and 94%, respectively, stable in human serum at 37°C for 2 h. (18)F-fluorobenzoate-R01 and (18)F-fluorobenzoate-S02 exhibited 2.3 ± 0.6 and 1.3 ± 0.4 percentage injected dose per gram (%ID/g), respectively, in BxPC3 xenografted tumors at 0.5 h (n = 4-5). Target specificity was confirmed by low tumor uptake in integrin ?v?6-negative 293 tumors (1.4 ± 0.6 and 0.5 ± 0.2 %ID/g, respectively, for (18)F-fluorobenzoate-R01 and (18)F-fluorobenzoate-S02; both P < 0.05; n = 3-4) and low muscle uptake (3.1 ± 1.0 and 2.7 ± 0.4 tumor to muscle for (18)F-fluorobenzoate-R01 and (18)F-fluorobenzoate-S02, respectively). Small-animal PET data were corroborated by ex vivo ?-counting of dissected tissues, which demonstrated low uptake in nontarget tissues with only modest kidney uptake (9.2 ± 3.3 and 1.9 ± 1.2 %ID/g, respectively, at 2 h for (18)F-fluorobenzoate-R01 and (18)F-fluorobenzoate-S02; n = 8). Uptake in healthy pancreas was low (0.3% ± 0.1% for (18)F-fluorobenzoate-R01 and 0.03% ± 0.01% for (18)F-fluorobenzoate-S02; n = 8).These cystine knot peptide tracers, in particular (18)F-fluorobenzoate-R01, show translational promise for molecular imaging of integrin ?v?6 overexpression in pancreatic and other cancers.

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Dataset Information

Fully automated ¹⁸F-fluorination of N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) for indirect labelling of nanobodies.

Publications

Fully automated <sup>18</sup>F-fluorination of N-succinimidyl-4-[<sup>18</sup>F]fluorobenzoate ([<sup>18</sup>F]SFB) for indirect labelling of nanobodies.

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