Imaging of human pancreatic cancer xenografts by single-photon emission computed tomography with 99mTc-Hynic-PEG-AE105

Abstract

Abstract. The elevated expression of urokinase-type plasminogen activator receptor (uPAR) is associated with the poor prognosis of pancreatic cancer patients. Thus, uPAR is a promising candidate as a molecular target for the non-invasive imaging of pancreatic cancer. The present study aimed to develop a technetium-99m ( 99m Tc)-labeled uPAR-binding peptide for non-invasive single-photon emission computed tomography (SPECT) assessment of uPAR expression in pancreatic cancer xenograft models. A linear high-affinity uPAR peptide antagonist, Hynic-PEG-AE105, was labeled with 99m Tc. Human uPAR-positive pancreatic cancer BxPC-3 cells were inoculated into nude mice. SPECT was performed in the pancreatic cancer xenograft mice models. The results showed that the rate of the 99m Tc labeling of Hynic-PEG-AE105 was 97.72±1.73%. The tumor uptake of 99m Tc-Hynic-PEG-AE105 was higher than the control inactive peptide 99m Tc-Hynic-PEG-AE105mut at 4 h (3.37±0.11 vs. 1.36±0.18; P<0.001) and 6 h (3.64±0.25 vs. 1.28±0.20; P<0.001) (n=10). Moreover, a significant correlation was observed between the tumor uptake of 99m Tc-Hynic-PEG-AE105 and uPAR expression (r= 0.791, P= 0.006). In conclusion, in the present study, a peptide-based SPECT tracer, 99m Tc-Hynic-PEG-AE105, with a high purity and specific radioactivity was synthesized. Tc-Hynic-PEG-AE105 is a promising agent for the non-invasive determination of uPAR expression in pancreatic cancer.

Molecular imaging of the urokinase plasminogen activator receptor: opportunities beyond cancer

“… n.v.t. In vitro preclinical [ 201 ] 99m Tc-Hynic-PEG-AE105 Peptide uPA-binding region SPECT 4-6 h In vivo preclinical [ 205 ] 64 Cu-DOTA-AE105 Peptide uPA-binding region PET 24 h Phase I clinical [ 13 , 219 – 222 , 224 ] 68 Ga-NOTA-AE105 Peptide uPA-binding region PET 10 min-1 h Phase I clinical [ 14 , 206 ] ICG-Glu-Glu-AE105 Peptide uPA-binding region Optical 6-24 h In vivo preclinical [ 207 – 209 ] CH1055-4Glu-AE105 Peptide uPA-binding region Optical 72-96 h In vivo preclinical [ 210 ] AF680-2G10 Antibody uPA-binding region Optical 48-96 h Recombinant antibody with trastuzumab Fc region In vivo preclinical [ 211 , 212 ] 111 ln-2G10 Antibody uPA-binding region SPECT 48-120 h Recombinant antibody with trastuzumab Fc region In vivo preclinical [ 211 , 212 ] AF680-3C6 Antibody β1-binding region Optical 48-96 h …”

“…This peptide, AE105, is the refined version of a 15-mer peptide identified by a phage display with uPAR-transfected cell lines and binds uPAR at the uPA-binding site in a species specific manner, like ATF [ 217 , 218 ]. While AE105 has also been conjugated with (radio)-labels for single-photon emission computed tomography (SPECT) and near-infrared fluorescence (NIRF) in preclinical oncology studies, this section will focus on positron-emission tomography as AE105 PET is further along the clinical pipeline [ 205 – 210 , 219 , 220 ]. Initially, AE105 has been conjugated with the metal chelator DOTA and subsequently labeled with 64 Cu.…”