Details

Autor(en) / Beteiligte

• Jagoda, Elaine M
• Bhattacharyya, Sibaprasad
• Kalen, Joseph
• Riffle, Lisa
• Leeder, Avrum
• Histed, Stephanie
• Williams, Mark
• Wong, Karen J
• Xu, Biying
• Szajek, Lawrence P
• Elbuluk, Osama
• Cecchi, Fabiola
• Raffensperger, Kristen
• Golla, Meghana
• Bottaro, Donald P
• Choyke, Peter

Titel

Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [ 99m Tc] (AH-113018) or CY 5 (AH-112543) Labeled Peptide

Ist Teil von

• Molecular imaging, 2015-09, Vol.14 (9), p.7290201500023

Ort / Verlag

United States

Erscheinungsjahr

2015

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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 [ Tc] had high affinity in vitro (K = 3.3 nM) and detected relative changes in Met in human cancer cell lines. In vivo [ 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 [ Tc]-Met peptide imaging and measurement of tumor volumes. Tumor uptake of [" 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. [ 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 [ Tc] or Cy5**-Met peptide imaging may have clinical diagnostic, prognostic, and therapeutic monitoring applications.