⁹⁹Tc^m-3PRGD₂ for Integrin Receptor Imaging of Pancreatic Cancer: Experimental Study on Tumor Bearing Nude Mice and Clinical Transformation Research

To evaluate an integrin imaging approach based on single photon emission computed tomography(SPECT) by using a technetium-99m(⁹⁹Tc^m) labeled dimeric cyclic arginine-glycine-aspartic acid(RGD) analogue(3PRGD₂) as the tracer to target the integrin α_vβ₃ expressed pancreatic cancer. PANC-1 pancreatic cancer cells and tumor tissues were stained with integrin α_vβ₃ to find if it is operatively expressed. PANC-1 pancreatic cancer cells were implanted into the shoulder of BALB/C nude mice to establish a qualified animal model. ⁹⁹Tc^m-3PRGD₂ was prepared with hydrazine nicotinamide(HYNIC) as a dual functional linker. ⁹⁹Tc^m-3PRGD₂ whole body planar imaging was performed every 0.5 hours to observe the distribution of the whole body. ROIs(regions of interest) were drawn on the tumor and the healthy side, and the ratios of tumor to background were calculated. ⁹⁹Tc^m-3PRGD₂ SPECT was performed in 6 patients with pancreatic tumor to evaluate the detection efficiency of pancreatic cancer. Integrin α_vβ₃ is highly expressed in PANC-1 pancreatic cancer cells and tumor tissues. The labeling rate of ⁹⁹Tc^m-3PRGD₂ is more than 99%. The imaging of tumor bearing mice show that the tumor has a high uptake of the tracer, and the tumor can be seen in 0.5 h p.i., the T/NT reachs the maximum value in 1.5 h p.i., and the tumor can be clearly displayed in 6.0 hours. ⁹⁹Tc^m-3PRGD₂ SPECT can detect primary pancreatic lesions and liver metastases in 6 patients, with a detection rate of 100%. ⁹⁹Tc^m-3PRGD₂ imaging is sensitive for the detection of pancreatic cancer, meriting further investigation of ⁹⁹Tc^m-3PRGD₂ as a novel clinical tracer for integrin receptor imaging.