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Meningiomas: a comparative study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for molecular imaging in mice.

Soto-Montenegro ML, Peña-Zalbidea S, Mateos-Pérez JM, Oteo M, Romero E, Morcillo MÁ, Desco M - PLoS ONE (2014)

Bottom Line: No significant differences between tracers were found for SUVmax in tumor or muscle.No differences were found in the T/L SUV ratio between (68)Ga-DOTATATE and (68)Ga-DOTATOC, both of which had a higher fraction than (68)Ga-DOTANOC.The T/M SUV ratio was significantly higher with (68)Ga-DOTATATE than with (68)Ga-DOTATOC and (68)Ga-DOTANOC.

View Article: PubMed Central - PubMed

Affiliation: Unidad de Medicina y Cirugía Experimental, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.

ABSTRACT

Purpose: The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three (68)Ga-DOTA-labeled somatostatin analogues ((68)Ga-DOTATOC, (68)Ga-DOTANOC, and (68)Ga-DOTATATE) using PET/CT in a murine model with subcutaneous meningioma xenografts.

Methods: The experiment was performed with 16 male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH-157MN). (68)Ga-DOTATOC, (68)Ga-DOTANOC, and (68)Ga-DOTATATE were produced in a FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT scanner. The SUVmax of the liver and muscle, and the tumor-to-liver (T/L) and tumor-to-muscle (T/M) SUV ratios were computed. Kinetic analysis was performed using Logan graphical analysis for a two-tissue reversible compartmental model, and the volume of distribution (Vt) was determined.

Results: Hepatic SUVmax and Vt were significantly higher with (68)Ga-DOTANOC than with (68)Ga-DOTATOC and (68)Ga-DOTATATE. No significant differences between tracers were found for SUVmax in tumor or muscle. No differences were found in the T/L SUV ratio between (68)Ga-DOTATATE and (68)Ga-DOTATOC, both of which had a higher fraction than (68)Ga-DOTANOC. The T/M SUV ratio was significantly higher with (68)Ga-DOTATATE than with (68)Ga-DOTATOC and (68)Ga-DOTANOC. The Vt for tumor was higher with (68)Ga-DOTATATE than with (68)Ga-DOTANOC and relatively similar to that of (68)Ga-DOTATOC.

Conclusions: This study demonstrates, for the first time, the ability of the three radiolabeled somatostatin analogues tested to image a human meningioma cell line. Although Vt was relatively similar with (68)Ga-DOTATATE and (68)Ga-DOTATOC, uptake was higher with (68)Ga-DOTATATE in the tumor than with (68)Ga-DOTANOC and (68)Ga-DOTATOC, suggesting a higher diagnostic value of (68)Ga-DOTATATE for detecting meningiomas.

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SSTR affinity and immunohistochemistry studies.A) Competitive binding of [125I]-Somatostatin-28 to CH-57MN cells incubated at 37°C. IC50 and maximum numbers of binding sites (Bmax) were calculated using Origin 7.5 software. Data are from three independent experiments performed in triplicate (Mean ± SEM). B) Immunohistochemistry using SSTR2 antibody (original magnification, x20). Tumor obtained from the CH-157MN cell line.
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pone-0111624-g002: SSTR affinity and immunohistochemistry studies.A) Competitive binding of [125I]-Somatostatin-28 to CH-57MN cells incubated at 37°C. IC50 and maximum numbers of binding sites (Bmax) were calculated using Origin 7.5 software. Data are from three independent experiments performed in triplicate (Mean ± SEM). B) Immunohistochemistry using SSTR2 antibody (original magnification, x20). Tumor obtained from the CH-157MN cell line.

Mentions: Figure 2A shows the high binding affinity of SSTR in CH-157MN cells for the universal ligand somatostatin-28. The IC50 was 63.7±32.3 nM and the Bmax was 78.4±6.5 fmol/106 cells.


Meningiomas: a comparative study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for molecular imaging in mice.

Soto-Montenegro ML, Peña-Zalbidea S, Mateos-Pérez JM, Oteo M, Romero E, Morcillo MÁ, Desco M - PLoS ONE (2014)

SSTR affinity and immunohistochemistry studies.A) Competitive binding of [125I]-Somatostatin-28 to CH-57MN cells incubated at 37°C. IC50 and maximum numbers of binding sites (Bmax) were calculated using Origin 7.5 software. Data are from three independent experiments performed in triplicate (Mean ± SEM). B) Immunohistochemistry using SSTR2 antibody (original magnification, x20). Tumor obtained from the CH-157MN cell line.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219730&req=5

pone-0111624-g002: SSTR affinity and immunohistochemistry studies.A) Competitive binding of [125I]-Somatostatin-28 to CH-57MN cells incubated at 37°C. IC50 and maximum numbers of binding sites (Bmax) were calculated using Origin 7.5 software. Data are from three independent experiments performed in triplicate (Mean ± SEM). B) Immunohistochemistry using SSTR2 antibody (original magnification, x20). Tumor obtained from the CH-157MN cell line.
Mentions: Figure 2A shows the high binding affinity of SSTR in CH-157MN cells for the universal ligand somatostatin-28. The IC50 was 63.7±32.3 nM and the Bmax was 78.4±6.5 fmol/106 cells.

Bottom Line: No significant differences between tracers were found for SUVmax in tumor or muscle.No differences were found in the T/L SUV ratio between (68)Ga-DOTATATE and (68)Ga-DOTATOC, both of which had a higher fraction than (68)Ga-DOTANOC.The T/M SUV ratio was significantly higher with (68)Ga-DOTATATE than with (68)Ga-DOTATOC and (68)Ga-DOTANOC.

View Article: PubMed Central - PubMed

Affiliation: Unidad de Medicina y Cirugía Experimental, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.

ABSTRACT

Purpose: The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three (68)Ga-DOTA-labeled somatostatin analogues ((68)Ga-DOTATOC, (68)Ga-DOTANOC, and (68)Ga-DOTATATE) using PET/CT in a murine model with subcutaneous meningioma xenografts.

Methods: The experiment was performed with 16 male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH-157MN). (68)Ga-DOTATOC, (68)Ga-DOTANOC, and (68)Ga-DOTATATE were produced in a FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT scanner. The SUVmax of the liver and muscle, and the tumor-to-liver (T/L) and tumor-to-muscle (T/M) SUV ratios were computed. Kinetic analysis was performed using Logan graphical analysis for a two-tissue reversible compartmental model, and the volume of distribution (Vt) was determined.

Results: Hepatic SUVmax and Vt were significantly higher with (68)Ga-DOTANOC than with (68)Ga-DOTATOC and (68)Ga-DOTATATE. No significant differences between tracers were found for SUVmax in tumor or muscle. No differences were found in the T/L SUV ratio between (68)Ga-DOTATATE and (68)Ga-DOTATOC, both of which had a higher fraction than (68)Ga-DOTANOC. The T/M SUV ratio was significantly higher with (68)Ga-DOTATATE than with (68)Ga-DOTATOC and (68)Ga-DOTANOC. The Vt for tumor was higher with (68)Ga-DOTATATE than with (68)Ga-DOTANOC and relatively similar to that of (68)Ga-DOTATOC.

Conclusions: This study demonstrates, for the first time, the ability of the three radiolabeled somatostatin analogues tested to image a human meningioma cell line. Although Vt was relatively similar with (68)Ga-DOTATATE and (68)Ga-DOTATOC, uptake was higher with (68)Ga-DOTATATE in the tumor than with (68)Ga-DOTANOC and (68)Ga-DOTATOC, suggesting a higher diagnostic value of (68)Ga-DOTATATE for detecting meningiomas.

Show MeSH
Related in: MedlinePlus