In Vitro and In Vivo Characterization of Three Ga- and In-Labeled Peptides for Cholecystokinin Receptor Imaging
Cholecystokinin (CCK) receptors are overexpressed in several human tumor types, such as medullary thyroid carcinomas and small cell lung cancers. Several ligands for the CCK2 receptor (CCK2R) have been developed for radionuclide targeting of these tumors. In this study, we evaluated whether radiolab...
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SAGE Publishing
2012-09-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2012.00001 |
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| author | Susan Roosenburg Peter Laverman Lieke Joosten Annemarie Eek Floris P.J.T. Rutjes Floris L. van Delft Otto C. Boerman |
| author_facet | Susan Roosenburg Peter Laverman Lieke Joosten Annemarie Eek Floris P.J.T. Rutjes Floris L. van Delft Otto C. Boerman |
| author_sort | Susan Roosenburg |
| collection | DOAJ |
| description | Cholecystokinin (CCK) receptors are overexpressed in several human tumor types, such as medullary thyroid carcinomas and small cell lung cancers. Several ligands for the CCK2 receptor (CCK2R) have been developed for radionuclide targeting of these tumors. In this study, we evaluated whether radiolabeled DOTA-sCCK8 and its stabilized derivative, DOTA-sCCK8[Phe 2 (p-CH 2 SO 3 H), Nle 3,6 ], are suitable for imaging of CCK2R-positive tumors, using DOTA-MG0 as a reference. In vivo targeting of CCK2R-positive tumors with DOTA-sCCK8, DOTA-sCCK8[Phe 2 ( p -CH 2 SO 3 H), Nle 3,6 ], and DOTA-MG0, labeled with 111 In or 68 Ga, was evaluated in BALB/c nude mice with a subcutaneous A431-CCK2R tumor. Biodistribution studies and single-photon emission computed tomography (SPECT) and positron emission tomography (PET) were performed at 1 hour postinjection. All peptides specifically accreted in the CCK2R-expressing tumors. Both 111 In-DOTA-sCCK8 and 111 In-DOTA-sCCK8[Phe 2 ( p -CH 2 SO 3 H), Nle 3,6 ] showed good tumor retention (4.65% ID/g and 5.44% ID/g, respectively, at 4 hours postinjection). On PET/computed tomographic (CT) and SPECT/CT scans, subcutaneous A431-CCK2R tumors were clearly visualized with low uptake of sCCK8 peptides in the intestines. Whereas radiolabeled DOTA-MG0 showed high kidney uptake (70% ID/g), the sCCK8 peptides showed low uptake in the kidneys. Sulfated CCK8 analogues combined high tumor uptake with low retention in the kidney and are therefore promising tracers for imaging of CCK2R-positive tumors. |
| format | Article |
| id | doaj-art-e893be429ff94600bd631e0fd8ad4ecd |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2012-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-e893be429ff94600bd631e0fd8ad4ecd2025-01-03T00:11:14ZengSAGE PublishingMolecular Imaging1536-01212012-09-011110.2310/7290.2012.0000110.2310_7290.2012.00001In Vitro and In Vivo Characterization of Three Ga- and In-Labeled Peptides for Cholecystokinin Receptor ImagingSusan RoosenburgPeter LavermanLieke JoostenAnnemarie EekFloris P.J.T. RutjesFloris L. van DelftOtto C. BoermanCholecystokinin (CCK) receptors are overexpressed in several human tumor types, such as medullary thyroid carcinomas and small cell lung cancers. Several ligands for the CCK2 receptor (CCK2R) have been developed for radionuclide targeting of these tumors. In this study, we evaluated whether radiolabeled DOTA-sCCK8 and its stabilized derivative, DOTA-sCCK8[Phe 2 (p-CH 2 SO 3 H), Nle 3,6 ], are suitable for imaging of CCK2R-positive tumors, using DOTA-MG0 as a reference. In vivo targeting of CCK2R-positive tumors with DOTA-sCCK8, DOTA-sCCK8[Phe 2 ( p -CH 2 SO 3 H), Nle 3,6 ], and DOTA-MG0, labeled with 111 In or 68 Ga, was evaluated in BALB/c nude mice with a subcutaneous A431-CCK2R tumor. Biodistribution studies and single-photon emission computed tomography (SPECT) and positron emission tomography (PET) were performed at 1 hour postinjection. All peptides specifically accreted in the CCK2R-expressing tumors. Both 111 In-DOTA-sCCK8 and 111 In-DOTA-sCCK8[Phe 2 ( p -CH 2 SO 3 H), Nle 3,6 ] showed good tumor retention (4.65% ID/g and 5.44% ID/g, respectively, at 4 hours postinjection). On PET/computed tomographic (CT) and SPECT/CT scans, subcutaneous A431-CCK2R tumors were clearly visualized with low uptake of sCCK8 peptides in the intestines. Whereas radiolabeled DOTA-MG0 showed high kidney uptake (70% ID/g), the sCCK8 peptides showed low uptake in the kidneys. Sulfated CCK8 analogues combined high tumor uptake with low retention in the kidney and are therefore promising tracers for imaging of CCK2R-positive tumors.https://doi.org/10.2310/7290.2012.00001 |
| spellingShingle | Susan Roosenburg Peter Laverman Lieke Joosten Annemarie Eek Floris P.J.T. Rutjes Floris L. van Delft Otto C. Boerman In Vitro and In Vivo Characterization of Three Ga- and In-Labeled Peptides for Cholecystokinin Receptor Imaging Molecular Imaging |
| title | In Vitro and In Vivo Characterization of Three Ga- and In-Labeled Peptides for Cholecystokinin Receptor Imaging |
| title_full | In Vitro and In Vivo Characterization of Three Ga- and In-Labeled Peptides for Cholecystokinin Receptor Imaging |
| title_fullStr | In Vitro and In Vivo Characterization of Three Ga- and In-Labeled Peptides for Cholecystokinin Receptor Imaging |
| title_full_unstemmed | In Vitro and In Vivo Characterization of Three Ga- and In-Labeled Peptides for Cholecystokinin Receptor Imaging |
| title_short | In Vitro and In Vivo Characterization of Three Ga- and In-Labeled Peptides for Cholecystokinin Receptor Imaging |
| title_sort | in vitro and in vivo characterization of three ga and in labeled peptides for cholecystokinin receptor imaging |
| url | https://doi.org/10.2310/7290.2012.00001 |
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