Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [Tc] (AH-113018) or CY 5** (AH-112543) Labeled Peptide
Developing an imaging agent targeting the hepatocyte growth factor receptor protein (Met) status of cancerous lesions would aid in the diagnosis and monitoring of Met-targeted tyrosine kinase inhibitors (TKIS). A peptide targeting Met labeled with [ 99m Tc] had high affinity in vitro (K d = 3.3 nM)...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2015-09-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2015.00023 |
| _version_ | 1797288057057050624 |
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| author | Elaine M. Jagoda Sibaprasad Bhattacharyya Joseph Kalen Lisa Riffle Avrum Leeder Stephanie Histed Mark Williams Karen J. Wong Biying Xu Lawrence P. Szajek Osama Elbuluk Fabiola Cecchi Kristen Raffensperger Meghana Golla Donald P. Bottaro Peter Choyke |
| author_facet | Elaine M. Jagoda Sibaprasad Bhattacharyya Joseph Kalen Lisa Riffle Avrum Leeder Stephanie Histed Mark Williams Karen J. Wong Biying Xu Lawrence P. Szajek Osama Elbuluk Fabiola Cecchi Kristen Raffensperger Meghana Golla Donald P. Bottaro Peter Choyke |
| author_sort | Elaine M. Jagoda |
| collection | DOAJ |
| description | Developing an imaging agent targeting the hepatocyte growth factor receptor protein (Met) status of cancerous lesions would aid in the diagnosis and monitoring of Met-targeted tyrosine kinase inhibitors (TKIS). A peptide targeting Met labeled with [ 99m Tc] had high affinity in vitro (K d = 3.3 nM) and detected relative changes in Met in human cancer cell lines. In vivo [ 99m Tc]-Met peptide (AH-113018) was retained in Met-expressing tumors, and high-expressing Met tumors (MKN-45) were easily visualized and quantitated using singlephoton emission computed tomography or optical imaging. In further studies, MKN-45 mouse xenografts treated with PHA 665752 (Met TKI) or vehicle were monitored weekly for tumor responses by [ 99m Tc]-Met peptide imaging and measurement of tumor volumes. Tumor uptake of [“ m Tc]-Met peptide was significantly decreased as early as 1 week after PHA 665752 treatment, corresponding to decreases in tumor volumes. These results were comparable to Cy5**-Met peptide (AH-112543) fluorescence imaging using the same treatment model. [ 99m Tc] or Cy5**-Met peptide tumor uptake was further validated by histologic (necrosis, apoptosis) and immunoassay (total Met, p Met, and plasma shed Met) assessments in imaged and nonimaged cohorts. These data suggest that [ 99m Tc] or Cy5**-Met peptide imaging may have clinical diagnostic, prognostic, and therapeutic monitoring applications. |
| first_indexed | 2024-03-07T18:43:48Z |
| format | Article |
| id | doaj.art-b4b698de7cb6463c8bfdf88a43f902f0 |
| institution | Directory Open Access Journal |
| issn | 1536-0121 |
| language | English |
| last_indexed | 2024-03-07T18:43:48Z |
| publishDate | 2015-09-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj.art-b4b698de7cb6463c8bfdf88a43f902f02024-03-02T03:15:50ZengSAGE PublicationsMolecular Imaging1536-01212015-09-011410.2310/7290.2015.0002310.2310_7290.2015.00023Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [Tc] (AH-113018) or CY 5** (AH-112543) Labeled PeptideElaine M. JagodaSibaprasad BhattacharyyaJoseph KalenLisa RiffleAvrum LeederStephanie HistedMark WilliamsKaren J. WongBiying XuLawrence P. SzajekOsama ElbulukFabiola CecchiKristen RaffenspergerMeghana GollaDonald P. BottaroPeter ChoykeDeveloping an imaging agent targeting the hepatocyte growth factor receptor protein (Met) status of cancerous lesions would aid in the diagnosis and monitoring of Met-targeted tyrosine kinase inhibitors (TKIS). A peptide targeting Met labeled with [ 99m Tc] had high affinity in vitro (K d = 3.3 nM) and detected relative changes in Met in human cancer cell lines. In vivo [ 99m Tc]-Met peptide (AH-113018) was retained in Met-expressing tumors, and high-expressing Met tumors (MKN-45) were easily visualized and quantitated using singlephoton emission computed tomography or optical imaging. In further studies, MKN-45 mouse xenografts treated with PHA 665752 (Met TKI) or vehicle were monitored weekly for tumor responses by [ 99m Tc]-Met peptide imaging and measurement of tumor volumes. Tumor uptake of [“ m Tc]-Met peptide was significantly decreased as early as 1 week after PHA 665752 treatment, corresponding to decreases in tumor volumes. These results were comparable to Cy5**-Met peptide (AH-112543) fluorescence imaging using the same treatment model. [ 99m Tc] or Cy5**-Met peptide tumor uptake was further validated by histologic (necrosis, apoptosis) and immunoassay (total Met, p Met, and plasma shed Met) assessments in imaged and nonimaged cohorts. These data suggest that [ 99m Tc] or Cy5**-Met peptide imaging may have clinical diagnostic, prognostic, and therapeutic monitoring applications.https://doi.org/10.2310/7290.2015.00023 |
| spellingShingle | Elaine M. Jagoda Sibaprasad Bhattacharyya Joseph Kalen Lisa Riffle Avrum Leeder Stephanie Histed Mark Williams Karen J. Wong Biying Xu Lawrence P. Szajek Osama Elbuluk Fabiola Cecchi Kristen Raffensperger Meghana Golla Donald P. Bottaro Peter Choyke Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [Tc] (AH-113018) or CY 5** (AH-112543) Labeled Peptide Molecular Imaging |
| title | Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [Tc] (AH-113018) or CY 5** (AH-112543) Labeled Peptide |
| title_full | Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [Tc] (AH-113018) or CY 5** (AH-112543) Labeled Peptide |
| title_fullStr | Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [Tc] (AH-113018) or CY 5** (AH-112543) Labeled Peptide |
| title_full_unstemmed | Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [Tc] (AH-113018) or CY 5** (AH-112543) Labeled Peptide |
| title_short | Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [Tc] (AH-113018) or CY 5** (AH-112543) Labeled Peptide |
| title_sort | imaging the met receptor tyrosine kinase met and assessing tumor responses to a met tyrosine kinase inhibitor in human xenograft mouse models with a tc ah 113018 or cy 5 ah 112543 labeled peptide |
| url | https://doi.org/10.2310/7290.2015.00023 |
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