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Molecular Cancer Therapeutics
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Pretargeted Immuno–Positron Emission Tomography Imaging of Carcinoembryonic Antigen–Expressing Tumors with a Bispecific Antibody and a 68Ga- and 18F-Labeled Hapten Peptide in Mice with Human Tumor Xenografts

Rafke Schoffelen, Robert M. Sharkey, David M. Goldenberg, Gerben Franssen, William J. McBride, Edmund A. Rossi, Chien-Hsing Chang, Peter Laverman, Jonathan A. Disselhorst, Annemarie Eek, Winette T.A. van der Graaf, Wim J.G. Oyen and Otto C. Boerman
Rafke Schoffelen
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Robert M. Sharkey
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David M. Goldenberg
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Gerben Franssen
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William J. McBride
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Edmund A. Rossi
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Chien-Hsing Chang
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Peter Laverman
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Jonathan A. Disselhorst
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Annemarie Eek
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Winette T.A. van der Graaf
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Wim J.G. Oyen
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Otto C. Boerman
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DOI: 10.1158/1535-7163.MCT-09-0862 Published April 2010
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    Figure 1.

    Chemical structures of IMP-288 and IMP-449. Both are Tyr-d-Lys-d-Glu-d-Lys tetrapeptides in which both lysine residues are substituted with a HSG moiety via their ε-amino group. IMP-288 is conjugated with DOTA, and IMP-449 is conjugated with NOTA.

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    Figure 2.

    Biodistribution of 111In-IMP-288 1 h after i.v. injection, following pretargeting with escalating doses of TF2 in BALB/c nude mice with a s.c. CEA-expressing LS174T tumor. Two peptide doses were tested: 0.01 nmol 111In-IMP-288 (A) and 0.10 nmol 111In-IMP-288 (B). Values are given as means ± SD (n = 5).

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    Figure 3.

    A, biodistribution of 6.0 nmol 125I-TF2 (0.37 MBq) and 0.25 nmol 68Ga-IMP-288 (5 MBq) 1 h after i.v. injection of 68Ga-IMP-288 in BALB/c nude mice with a s.c. LS174T and SK-RC 52 tumor. Values are given as means ± SD (n = 5). B, three-dimensional volume rendering of PET/CT image of a BALB/c nude mouse with a s.c. LS174T CEA-expressing tumor in the right flank (arrow) and a s.c. SK-RC 52 tumor, a non–CEA-producing tumor, in the left flank (arrowhead), which received 6.0 nmol TF2 and 5 MBq 68Ga-IMP-288 (0.25 nmol) i.v. with a 16-h interval, imaged 1 h after 68Ga-IMP-288 injection.

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    Figure 4.

    PET/CT images of a BALB/c nude mouse with a s.c. LS174T tumor (0.1 g) on the right hind leg (arrow) and an inflammation in the left thigh muscle (arrowhead), which received 5 MBq 18F-FDG and, 1 d later, 6.0 nmol TF2 and 5 MBq 68Ga-IMP-288 (0.25 nmol) with a 16-h interval. The animal was imaged 1 h after 18F-FDG and 68Ga-IMP-288 injections. The panel shows the three-dimensional volume rendering of the pretargeted immuno-PET scan (A) and the FDG-PET scan (B), and the transverse sections of the tumor region of the pretargeted immuno-PET scan (C) and the FDG-PET scan (D).

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    Figure 5.

    Biodistribution of 5 MBq FDG and 5 MBq 68Ga-IMP-288 (0.25 nmol) 1 h after injection, following pretargeting with 6.0 nmol TF2 in BALB/c nude mice with a s.c. CEA-expressing LS174T tumor. Values are given as means ± SD (n = 5).

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    Figure 6.

    Biodistribution of 0.25 nmol 18F-IMP-449 (5 MBq) 1 h after injection, following pretargeting with 6.0 nmol TF2 16 h earlier, biodistribution of 18F-IMP-449 without pretargeting, or biodistribution of Al[18F]2+ in BALB/c nude mice with a s.c. CEA-expressing LS174T tumor. Values are given as means ± SD.

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    Figure 7.

    Static PET/CT imaging study of a BALB/c nude mouse with a s.c. LS174T tumor (0.1 g) on the right side, which received 6.0 nmol TF2 and 0.25 nmol 18F-IMP-449 (5 MBq) i.v. with a 16-h interval. The animal was imaged 1 h after injection of 18F-IMP-449. The panel shows the three-dimensional volume rendering (posterior view; A) and cross-sections at the tumor region [coronal (B), sagittal (C), and transversal (D)].

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Molecular Cancer Therapeutics: 9 (4)
April 2010
Volume 9, Issue 4
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Pretargeted Immuno–Positron Emission Tomography Imaging of Carcinoembryonic Antigen–Expressing Tumors with a Bispecific Antibody and a 68Ga- and 18F-Labeled Hapten Peptide in Mice with Human Tumor Xenografts
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Pretargeted Immuno–Positron Emission Tomography Imaging of Carcinoembryonic Antigen–Expressing Tumors with a Bispecific Antibody and a 68Ga- and 18F-Labeled Hapten Peptide in Mice with Human Tumor Xenografts
Rafke Schoffelen, Robert M. Sharkey, David M. Goldenberg, Gerben Franssen, William J. McBride, Edmund A. Rossi, Chien-Hsing Chang, Peter Laverman, Jonathan A. Disselhorst, Annemarie Eek, Winette T.A. van der Graaf, Wim J.G. Oyen and Otto C. Boerman
Mol Cancer Ther April 1 2010 (9) (4) 1019-1027; DOI: 10.1158/1535-7163.MCT-09-0862

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Pretargeted Immuno–Positron Emission Tomography Imaging of Carcinoembryonic Antigen–Expressing Tumors with a Bispecific Antibody and a 68Ga- and 18F-Labeled Hapten Peptide in Mice with Human Tumor Xenografts
Rafke Schoffelen, Robert M. Sharkey, David M. Goldenberg, Gerben Franssen, William J. McBride, Edmund A. Rossi, Chien-Hsing Chang, Peter Laverman, Jonathan A. Disselhorst, Annemarie Eek, Winette T.A. van der Graaf, Wim J.G. Oyen and Otto C. Boerman
Mol Cancer Ther April 1 2010 (9) (4) 1019-1027; DOI: 10.1158/1535-7163.MCT-09-0862
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Molecular Cancer Therapeutics
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