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Prospective Study of (68)Ga-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers and First Application in Glioma Patients.

Wang Z, Zhang M, Wang L, Wang S, Kang F, Li G, Jacobson O, Niu G, Yang W, Wang J, Chen X - Theranostics (2015)

Bottom Line: The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining. (68)Ga-NOTA-NFB was safe and well tolerated by all subjects.The mean effective dose was 25.4 ± 6.1 μSv/MBq.The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent (68)Ga-NOTA-NFB uptake.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

ABSTRACT

Purpose: The chemokine receptor CXCR4 is overexpressed in various types of human cancers. As a specific imaging agent of CXCR4, (68)Ga-NOTA-NFB was investigated in this study to assess its safety, biodistribution and dosimetry properties in healthy volunteers, and to preliminarily evaluate its application in glioma patients.

Methods: Six healthy volunteers underwent whole-body PET scans at 0, 0.5, 1, 2 and 3 h after (68)Ga-NOTA-NFB injection (mean dose, 182.4 ± 3.7 MBq (4.93 ± 0.10 mCi)). For time-activity curve calculations, 1 mL blood samples were obtained at 1, 3, 5, 10, 30, 60, 90, 120, 150 and 180 min after the injection. The estimated radiation doses were calculated by OLINDA/EXM software. Eight patients with glioma were enrolled and underwent both (68)Ga-NOTA-NFB and (18)F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining.

Results: (68)Ga-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity clearance from the blood circulation was observed. The organs with the highest absorbed doses were spleen (193.8 ± 32.5 μSv/MBq) and liver (119.3 ± 25.0 μSv/MBq). The mean effective dose was 25.4 ± 6.1 μSv/MBq. The maximum standardized uptake values (SUVmax) and the maximum target to non-target ratios (T/NTmax) of (68)Ga-NOTA-NFB PET/CT in glioma tissues were 4.11 ± 2.90 (range, 0.45-8.21) and 9.21 ± 8.75 (range, 3.66-24.88), respectively, while those of (18)F-FDG PET/CT were 7.34 ± 2.90 (range, 3.50-12.27) and 0.86 ± 0.41 (range, 0.35-1.59). The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent (68)Ga-NOTA-NFB uptake.

Conclusion: With a favorable radiation dosimetry profile, (68)Ga-NOTA-NFB is safe for clinical imaging. Compared to (18)F-FDG PET/CT, (68)Ga-NOTA-NFB PET/CT is more sensitive in detecting glioma and could have potential in diagnosing and treatment planning for CXCR4 positive patients.

No MeSH data available.


Related in: MedlinePlus

Structure of NOTA-NFB.
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Figure 1: Structure of NOTA-NFB.

Mentions: NOTA-NFB was synthesized according to a published procedure 13 using NOTA-NHS ester (CheMatech) as a chelator. 68Ga-NOTA-NFB (Figure 1) was synthesized by the following protocol: 50 μg of NOTA-NFB (5 μg/μL in deionized water) was added into a mixture of 50 μL of sodium acetate solution (1.25 M) and 1 mL of 68GaCl3 eluent (370-666 MBq, pH 1.3-1.5) obtained from a 68Ge/68Ga generator (ITG Co., Germany). The mixture was then heated at 100 ºC for 10 min. The reaction mixture was quenched by adding 10 mL of water and was then loaded onto a pre-activated C-18 Sep-pak Plus cartridge (500 mg, Waters). The cartridge was washed with an additional 6 mL of water. The radiolabeled peptide was eluted with 1 mL of 10 mM HCl/ethanol. The resulting solution was analyzed by instant thin-layer chromatography (ITLC, Bioscan, USA) and HPLC (Agilent Technologies 1200, USA). ITLC was performed with silica-gel paper strips (VARIAN) in a 1:1 mixture of methanol and sodium acetate developing solution. Analytical HPLC was performed on an Agilent Technologies 1200 system equipped with a RP C-18 column (ZORBAX, 5 µm, 4.6 × 250 mm). The HPLC method: solvent A consisted of 0.05% trifluoroacetic acid (TFA) in water, and Solvent B consisted of 0.05% TFA in acetonitrile with a flow rate of 1 mL/min. Gradient: 0-3 min, 5-5% solvent B; 3-20 min, 5-65% solvent B. The final 68Ga-NOTA-NFB solution was filtered with a 0.22 μm Millex-GP filter (EMD Millipore) before the injection.


Prospective Study of (68)Ga-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers and First Application in Glioma Patients.

Wang Z, Zhang M, Wang L, Wang S, Kang F, Li G, Jacobson O, Niu G, Yang W, Wang J, Chen X - Theranostics (2015)

Structure of NOTA-NFB.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4440444&req=5

Figure 1: Structure of NOTA-NFB.
Mentions: NOTA-NFB was synthesized according to a published procedure 13 using NOTA-NHS ester (CheMatech) as a chelator. 68Ga-NOTA-NFB (Figure 1) was synthesized by the following protocol: 50 μg of NOTA-NFB (5 μg/μL in deionized water) was added into a mixture of 50 μL of sodium acetate solution (1.25 M) and 1 mL of 68GaCl3 eluent (370-666 MBq, pH 1.3-1.5) obtained from a 68Ge/68Ga generator (ITG Co., Germany). The mixture was then heated at 100 ºC for 10 min. The reaction mixture was quenched by adding 10 mL of water and was then loaded onto a pre-activated C-18 Sep-pak Plus cartridge (500 mg, Waters). The cartridge was washed with an additional 6 mL of water. The radiolabeled peptide was eluted with 1 mL of 10 mM HCl/ethanol. The resulting solution was analyzed by instant thin-layer chromatography (ITLC, Bioscan, USA) and HPLC (Agilent Technologies 1200, USA). ITLC was performed with silica-gel paper strips (VARIAN) in a 1:1 mixture of methanol and sodium acetate developing solution. Analytical HPLC was performed on an Agilent Technologies 1200 system equipped with a RP C-18 column (ZORBAX, 5 µm, 4.6 × 250 mm). The HPLC method: solvent A consisted of 0.05% trifluoroacetic acid (TFA) in water, and Solvent B consisted of 0.05% TFA in acetonitrile with a flow rate of 1 mL/min. Gradient: 0-3 min, 5-5% solvent B; 3-20 min, 5-65% solvent B. The final 68Ga-NOTA-NFB solution was filtered with a 0.22 μm Millex-GP filter (EMD Millipore) before the injection.

Bottom Line: The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining. (68)Ga-NOTA-NFB was safe and well tolerated by all subjects.The mean effective dose was 25.4 ± 6.1 μSv/MBq.The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent (68)Ga-NOTA-NFB uptake.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

ABSTRACT

Purpose: The chemokine receptor CXCR4 is overexpressed in various types of human cancers. As a specific imaging agent of CXCR4, (68)Ga-NOTA-NFB was investigated in this study to assess its safety, biodistribution and dosimetry properties in healthy volunteers, and to preliminarily evaluate its application in glioma patients.

Methods: Six healthy volunteers underwent whole-body PET scans at 0, 0.5, 1, 2 and 3 h after (68)Ga-NOTA-NFB injection (mean dose, 182.4 ± 3.7 MBq (4.93 ± 0.10 mCi)). For time-activity curve calculations, 1 mL blood samples were obtained at 1, 3, 5, 10, 30, 60, 90, 120, 150 and 180 min after the injection. The estimated radiation doses were calculated by OLINDA/EXM software. Eight patients with glioma were enrolled and underwent both (68)Ga-NOTA-NFB and (18)F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining.

Results: (68)Ga-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity clearance from the blood circulation was observed. The organs with the highest absorbed doses were spleen (193.8 ± 32.5 μSv/MBq) and liver (119.3 ± 25.0 μSv/MBq). The mean effective dose was 25.4 ± 6.1 μSv/MBq. The maximum standardized uptake values (SUVmax) and the maximum target to non-target ratios (T/NTmax) of (68)Ga-NOTA-NFB PET/CT in glioma tissues were 4.11 ± 2.90 (range, 0.45-8.21) and 9.21 ± 8.75 (range, 3.66-24.88), respectively, while those of (18)F-FDG PET/CT were 7.34 ± 2.90 (range, 3.50-12.27) and 0.86 ± 0.41 (range, 0.35-1.59). The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent (68)Ga-NOTA-NFB uptake.

Conclusion: With a favorable radiation dosimetry profile, (68)Ga-NOTA-NFB is safe for clinical imaging. Compared to (18)F-FDG PET/CT, (68)Ga-NOTA-NFB PET/CT is more sensitive in detecting glioma and could have potential in diagnosing and treatment planning for CXCR4 positive patients.

No MeSH data available.


Related in: MedlinePlus