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Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging.

Liu Q, Pan D, Cheng C, Zhang D, Zhang A, Wang L, Jiang H, Wang T, Liu H, Xu Y, Yang R, Chen F, Yang M, Zuo C - PLoS ONE (2015)

Bottom Line: The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo.The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake.Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Changhai Hospital, the Second Military Medical University, Shanghai, 200433, China.

ABSTRACT

Background and objective: The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure.

Methods: C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo.

Results: The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues.

Conclusions: [18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors.

No MeSH data available.


Related in: MedlinePlus

Analytical HPLC profile of [18F]AlF-NOTA-C6 after incubation in human serum at 37°C for (A) 0, (B) 2, and (C) 4 h.
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pone.0141668.g005: Analytical HPLC profile of [18F]AlF-NOTA-C6 after incubation in human serum at 37°C for (A) 0, (B) 2, and (C) 4 h.

Mentions: The in vitro stability of [18F]AlF-NOTA-C6 was evaluated by radio-HPLC. As shown in Figs 4 and 5, after incubation in physiological saline at room temperature or in human serum at 37°C for 4 h, >95% of the radioactivity was observed in the form of [18F]AlF-NOTA-C6 (see S4 and S5 Figs). This analysis confirmed the absence of radioactive degradation products of [18F]AlF-NOTA-C6 at 2 and 4 h in physiological saline at room temperature or in human serum at 37°C.


Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging.

Liu Q, Pan D, Cheng C, Zhang D, Zhang A, Wang L, Jiang H, Wang T, Liu H, Xu Y, Yang R, Chen F, Yang M, Zuo C - PLoS ONE (2015)

Analytical HPLC profile of [18F]AlF-NOTA-C6 after incubation in human serum at 37°C for (A) 0, (B) 2, and (C) 4 h.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4634933&req=5

pone.0141668.g005: Analytical HPLC profile of [18F]AlF-NOTA-C6 after incubation in human serum at 37°C for (A) 0, (B) 2, and (C) 4 h.
Mentions: The in vitro stability of [18F]AlF-NOTA-C6 was evaluated by radio-HPLC. As shown in Figs 4 and 5, after incubation in physiological saline at room temperature or in human serum at 37°C for 4 h, >95% of the radioactivity was observed in the form of [18F]AlF-NOTA-C6 (see S4 and S5 Figs). This analysis confirmed the absence of radioactive degradation products of [18F]AlF-NOTA-C6 at 2 and 4 h in physiological saline at room temperature or in human serum at 37°C.

Bottom Line: The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo.The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake.Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Changhai Hospital, the Second Military Medical University, Shanghai, 200433, China.

ABSTRACT

Background and objective: The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [18F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure.

Methods: C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo.

Results: The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [18F]AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues.

Conclusions: [18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors.

No MeSH data available.


Related in: MedlinePlus