Publication

Evaluation of N-[C-11]Methyl-AMD3465 as a PET Tracer for Imaging of CXCR4 Receptor Expression in a C6 Glioma Tumor Model

Hartimath, S. V., van Waarde, A., Dierckx, R. A. J. O. & de Vries, E. F. J., Nov-2014, In : Molecular pharmaceutics. 11, 11, p. 3810-3817 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Hartimath, S. V., van Waarde, A., Dierckx, R. A. J. O., & de Vries, E. F. J. (2014). Evaluation of N-[C-11]Methyl-AMD3465 as a PET Tracer for Imaging of CXCR4 Receptor Expression in a C6 Glioma Tumor Model. Molecular pharmaceutics, 11(11), 3810-3817. https://doi.org/10.1021/mp500398r

Author

Hartimath, S. V. ; van Waarde, A. ; Dierckx, R. A. J. O. ; de Vries, E. F. J. / Evaluation of N-[C-11]Methyl-AMD3465 as a PET Tracer for Imaging of CXCR4 Receptor Expression in a C6 Glioma Tumor Model. In: Molecular pharmaceutics. 2014 ; Vol. 11, No. 11. pp. 3810-3817.

Harvard

Hartimath, SV, van Waarde, A, Dierckx, RAJO & de Vries, EFJ 2014, 'Evaluation of N-[C-11]Methyl-AMD3465 as a PET Tracer for Imaging of CXCR4 Receptor Expression in a C6 Glioma Tumor Model', Molecular pharmaceutics, vol. 11, no. 11, pp. 3810-3817. https://doi.org/10.1021/mp500398r

Standard

Evaluation of N-[C-11]Methyl-AMD3465 as a PET Tracer for Imaging of CXCR4 Receptor Expression in a C6 Glioma Tumor Model. / Hartimath, S. V.; van Waarde, A.; Dierckx, R. A. J. O.; de Vries, E. F. J.

In: Molecular pharmaceutics, Vol. 11, No. 11, 11.2014, p. 3810-3817.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Hartimath SV, van Waarde A, Dierckx RAJO, de Vries EFJ. Evaluation of N-[C-11]Methyl-AMD3465 as a PET Tracer for Imaging of CXCR4 Receptor Expression in a C6 Glioma Tumor Model. Molecular pharmaceutics. 2014 Nov;11(11):3810-3817. https://doi.org/10.1021/mp500398r


BibTeX

@article{020dd09a26b3469b92451f2bb8bb6e10,
title = "Evaluation of N-[C-11]Methyl-AMD3465 as a PET Tracer for Imaging of CXCR4 Receptor Expression in a C6 Glioma Tumor Model",
abstract = "The chemokine receptor CXCR4 and its ligand CXCL12 play an important role in tumor progression and metastasis. CXCR4 receptors are expressed by many cancer types and provide a potential target for treatment. Noninvasive detection of CXCR4 may aid diagnosis and improve therapy selection. It has been demonstrated in preclinical studies that positron emission tomography (PET) with a radiolabeled small molecule could enable noninvasive monitoring of CXCR4 expression. Here, we prepared N-[C-11]methyl-AMD3465 as a new PET tracer for CXCR4. N-[C-11]Methyl-AMD3465 was readily prepared by N-methylation with [C-11]CH3OTf. The tracer was obtained in a 60 +/- 2% yield (decay corrected), the purity of the tracer was >99%, and specific activity was 47 +/- 14 GBq/mu mol. Tracer stability was tested in vitro using liver microsomes and rat plasma; excellent stability was observed. The tracer was evaluated in rat C6 glioma and human PC-3 cell lines. In vitro cellular uptake of N-[C-11]methyl-AMD3465 was receptor mediated. The effect of transition metal ions (Cu2+, Ni2+, and Zn2+) on cellular binding was examined in C6 cells, and the presence of these ions increased the cellular binding of the tracer 9-, 7-, and 3-fold, respectively. Ex vivo biodistribution and PET imaging of N-[C-11]methyl-AMD3465 were performed in rats with C6 tumor xenografts. Both PET and biodistribution studies demonstrated specific accumulation of the tracer in the tumor (SUV 0.6 +/- 0.2) and other CXCR4 expressing organs, such as lymph node (1.5 +/- 0.2), liver (8.9 +/- 1.0), bone marrow (1.0 +/- 0.3), and spleen (1.0 +/- 0.1). Tumor uptake was significantly reduced (66%, p <0.01) after pretreatment with Plerixafor (AMD3100). Biodistribution data indicates a tumor-to-muscle ratio of 7.85 and tumor-to-plasma ratio of 1.14, at 60 min after tracer injection. Our data demonstrated that N-[C-11]methyl-AMD3465 is capable of detecting physiologic CXCR4 expression in tumors and other CXCR4 expressing tissues. These results warrant further evaluation of N-[C-11]methyl-AMD3465 as a potential PET tracer for CXCR4 receptor imaging.",
keywords = "chemokine receptor 4, tumor imaging, PET, AMD3465, cancer and metastasis, radiotracer, HUMAN CANCER XENOGRAFTS, CHEMOKINE RECEPTOR, BREAST-CANCER, ANTAGONIST, CELLS, MICROENVIRONMENT, METASTASIS, INHIBITION, MONOCYCLAM, BICYCLAM",
author = "Hartimath, {S. V.} and {van Waarde}, A. and Dierckx, {R. A. J. O.} and {de Vries}, {E. F. J.}",
year = "2014",
month = nov,
doi = "10.1021/mp500398r",
language = "English",
volume = "11",
pages = "3810--3817",
journal = "Molecular pharmaceutics",
issn = "1543-8384",
publisher = "AMER CHEMICAL SOC INC",
number = "11",

}

RIS

TY - JOUR

T1 - Evaluation of N-[C-11]Methyl-AMD3465 as a PET Tracer for Imaging of CXCR4 Receptor Expression in a C6 Glioma Tumor Model

AU - Hartimath, S. V.

AU - van Waarde, A.

AU - Dierckx, R. A. J. O.

AU - de Vries, E. F. J.

PY - 2014/11

Y1 - 2014/11

N2 - The chemokine receptor CXCR4 and its ligand CXCL12 play an important role in tumor progression and metastasis. CXCR4 receptors are expressed by many cancer types and provide a potential target for treatment. Noninvasive detection of CXCR4 may aid diagnosis and improve therapy selection. It has been demonstrated in preclinical studies that positron emission tomography (PET) with a radiolabeled small molecule could enable noninvasive monitoring of CXCR4 expression. Here, we prepared N-[C-11]methyl-AMD3465 as a new PET tracer for CXCR4. N-[C-11]Methyl-AMD3465 was readily prepared by N-methylation with [C-11]CH3OTf. The tracer was obtained in a 60 +/- 2% yield (decay corrected), the purity of the tracer was >99%, and specific activity was 47 +/- 14 GBq/mu mol. Tracer stability was tested in vitro using liver microsomes and rat plasma; excellent stability was observed. The tracer was evaluated in rat C6 glioma and human PC-3 cell lines. In vitro cellular uptake of N-[C-11]methyl-AMD3465 was receptor mediated. The effect of transition metal ions (Cu2+, Ni2+, and Zn2+) on cellular binding was examined in C6 cells, and the presence of these ions increased the cellular binding of the tracer 9-, 7-, and 3-fold, respectively. Ex vivo biodistribution and PET imaging of N-[C-11]methyl-AMD3465 were performed in rats with C6 tumor xenografts. Both PET and biodistribution studies demonstrated specific accumulation of the tracer in the tumor (SUV 0.6 +/- 0.2) and other CXCR4 expressing organs, such as lymph node (1.5 +/- 0.2), liver (8.9 +/- 1.0), bone marrow (1.0 +/- 0.3), and spleen (1.0 +/- 0.1). Tumor uptake was significantly reduced (66%, p <0.01) after pretreatment with Plerixafor (AMD3100). Biodistribution data indicates a tumor-to-muscle ratio of 7.85 and tumor-to-plasma ratio of 1.14, at 60 min after tracer injection. Our data demonstrated that N-[C-11]methyl-AMD3465 is capable of detecting physiologic CXCR4 expression in tumors and other CXCR4 expressing tissues. These results warrant further evaluation of N-[C-11]methyl-AMD3465 as a potential PET tracer for CXCR4 receptor imaging.

AB - The chemokine receptor CXCR4 and its ligand CXCL12 play an important role in tumor progression and metastasis. CXCR4 receptors are expressed by many cancer types and provide a potential target for treatment. Noninvasive detection of CXCR4 may aid diagnosis and improve therapy selection. It has been demonstrated in preclinical studies that positron emission tomography (PET) with a radiolabeled small molecule could enable noninvasive monitoring of CXCR4 expression. Here, we prepared N-[C-11]methyl-AMD3465 as a new PET tracer for CXCR4. N-[C-11]Methyl-AMD3465 was readily prepared by N-methylation with [C-11]CH3OTf. The tracer was obtained in a 60 +/- 2% yield (decay corrected), the purity of the tracer was >99%, and specific activity was 47 +/- 14 GBq/mu mol. Tracer stability was tested in vitro using liver microsomes and rat plasma; excellent stability was observed. The tracer was evaluated in rat C6 glioma and human PC-3 cell lines. In vitro cellular uptake of N-[C-11]methyl-AMD3465 was receptor mediated. The effect of transition metal ions (Cu2+, Ni2+, and Zn2+) on cellular binding was examined in C6 cells, and the presence of these ions increased the cellular binding of the tracer 9-, 7-, and 3-fold, respectively. Ex vivo biodistribution and PET imaging of N-[C-11]methyl-AMD3465 were performed in rats with C6 tumor xenografts. Both PET and biodistribution studies demonstrated specific accumulation of the tracer in the tumor (SUV 0.6 +/- 0.2) and other CXCR4 expressing organs, such as lymph node (1.5 +/- 0.2), liver (8.9 +/- 1.0), bone marrow (1.0 +/- 0.3), and spleen (1.0 +/- 0.1). Tumor uptake was significantly reduced (66%, p <0.01) after pretreatment with Plerixafor (AMD3100). Biodistribution data indicates a tumor-to-muscle ratio of 7.85 and tumor-to-plasma ratio of 1.14, at 60 min after tracer injection. Our data demonstrated that N-[C-11]methyl-AMD3465 is capable of detecting physiologic CXCR4 expression in tumors and other CXCR4 expressing tissues. These results warrant further evaluation of N-[C-11]methyl-AMD3465 as a potential PET tracer for CXCR4 receptor imaging.

KW - chemokine receptor 4

KW - tumor imaging

KW - PET

KW - AMD3465

KW - cancer and metastasis

KW - radiotracer

KW - HUMAN CANCER XENOGRAFTS

KW - CHEMOKINE RECEPTOR

KW - BREAST-CANCER

KW - ANTAGONIST

KW - CELLS

KW - MICROENVIRONMENT

KW - METASTASIS

KW - INHIBITION

KW - MONOCYCLAM

KW - BICYCLAM

U2 - 10.1021/mp500398r

DO - 10.1021/mp500398r

M3 - Article

C2 - 25094028

VL - 11

SP - 3810

EP - 3817

JO - Molecular pharmaceutics

JF - Molecular pharmaceutics

SN - 1543-8384

IS - 11

ER -

ID: 14256061