[^99mTc]labeled peptide targets the Met receptor tyrosine kinase (Met) in human gastric carcinoma (MKN 45) mouse xenografts

Objectives The overexpression of hepatocyte growth factor receptor protein (Met) in a variety of cancers has been linked to increased proliferation, progression to metastatic disease, drug resistance, and poor prognosis. Developing an imaging agent that could determine the Met status of cancerous lesions would aid in diagnosis as well as monitoring response to Met-targeted therapies. The pharmacokinetics and imaging potential of a [^99mTc]labeled Met-specific peptide ([^99mTc]), was evaluated in vitro in MKN and human glioblastoma [U87 MG (U87)] cells and in vivo in MKN xenografts.

Methods [^99mTc]Met was synthesized using [^99mTc]O₄- and a chelate kit method. [^99mTc]Met was evaluated in cell binding studies with MKN and U87 cells, high and low Met expression, respectively. Biodistribution and microSPECT/CT imaging studies were done at 30, 60, 90, and 120 min after [^99mTc]Met injections in MKN mouse xenografts.

Results High affinity binding (nM) of [^99mTc]Met was observed in both cell lines but MKN had greater specific binding and Met density than U87. Uptake of [^99mTc]Met in the MKN xenografts was rapid with the highest uptakes observed in tumor and kidney at all time points. MKN tumor uptake remained relatively constant from 30 to 60 min whereas a decrease of 36% and a further decrease of 13% were observed at 120 min and 180 min, respectively. High tumor:muscle ratios (T:M) of 10, 30, 50, and 55 were observed at 30, 60, 120, and 180 min, respectively. MKN tumors were visualized from imaging studies as early as 30 min and uptake in the tumors remained constant until 112 min, after which a 35% decrease was observed at 144 min.

Conclusions [^99mTc]Met was found to bind to Met with high affinity both in vitro and in vivo. The sustained retention of [^99mTc]Met in MKN tumors and the high T:M confirm these findings. These results suggest that [^99mTc]Met may have potential to image Met for diagnostic and prognostic purposes