Pancreatic Cancer detection via Galectin-1-targeted Thermoacoustic Imaging: validation in an in vivo heterozygosity model

Purpose: To investigate the feasibility of microwave-induced thermoacoustic imaging (MTAI) in detecting small pancreatic tumors (< 10 mm in diameter) and to complement the limitation of current clinical imaging methods. Methods: A home-made MTAI system composed of a portable antenna and pulsed microwave generator was developed. The thermoacoustic nanoparticles were composed of the galectin-1 antibody for targeting pancreatic tumors and Fe(3)O(4) nanoparticles as microwave absorbers (anti-Gal1-Fe(3)O(4) nanoparticles). The microwave absorption properties of the nanoparticles were measured with a vector network analyzer and the resolving power of MTAI was investigated by imaging excised pancreatic tumors of different sizes (diameters of 1.0 mm, 3.1 mm, 5.0 mm, 7.2 mm). To simulate actual imaging scenarios, an in vivo heterozygosity model was constructed by covering the pancreatic tumors (~ 3 mm in diameter) in BALB/c nude mice with biologic tissue (~ 5 cm in depth). MTAI images of the heterozygosity model were acquired with/without the injection of the anti-Gal1-Fe(3)O(4) nanoparticles and the thermoacoustic contrast from pancreatic tumors was evaluated with Student's paired t test. The data were analyzed with analysis of variance and nonparametric statistics. Results: Following intravenous infusion, anti-Gal1-Fe(3)O(4) nanoparticles efficiently accumulated in the tumor. The MTAI contrast enhancement in pancreatic tumors with anti-Gal1-Fe(3)O(4) nanoparticles was verified in vitro and in vivo. The pancreatic tumors were visible in nude mice examined with MTAI with a mean contrast enhancement ratio of 2.3 ± 0.15 (standard error of the mean) (P =. 001) at 6 h post-injection of the nanoparticles. MTAI identified tiny pancreatic tumors in deep tissues with high fidelity. Conclusion: MTAI offers deep imaging depth and high contrast when used with anti-Gal1-Fe(3)O(4) nanoparticles. It can identify pancreatic tumors smaller than 5 mm, which is beyond the identification limit size (~10 mm) of other nondestructive clinical imaging methods. Thus, MTAI has great potential as an alternative imaging modality for early pancreatic cancer detection.