# Targeted Molecular Imaging of Pancreatic Cancer with a Miniature Endoscope
## 1 Introduction  
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States (US). It is estimated that 53,670 new cases will be diagnosed and 43,090 pancreatic cancer patients will die in the US in 2017 [1]. The Pancreatic Cancer Action Network predicts that pancreatic malignancies will become the second leading cause of cancer-related death by 2020 [2]. In pancreatic cancer, the 5-year survival rate is approximately 7%, which is attributed to primary factors including inefficient early diagnostic tools and ineffective treatment methods. Nevertheless, the overall 5-year survival rate is significantly improved to 26% for patients diagnosed in the early stages without metastatic lesions [3]. Therefore, to develop reliable methods that can improve early diagnosis is highly desired.  
Conventional diagnostic imaging modalities including X-ray radiography, computed tomography (CT), fluoroscopy, ultrasonography, and magnetic resonance imaging (MRI) have been used for diagnosis and treatment planning for pancreatic cancer medically. However, these conventional imaging modalities provide only structural or anatomical changes, which often happen several years after detrimental molecular changes, especially for pancreas-related diseases. The specificity of these conventional imaging techniques for the early diagnosis of pancreatic cancer is quite low [4].  
It is believed that molecular imaging is able to offer highly sensitive and specific detection of tumors through sensing molecular changes. For pancreatic cancer, current existing molecular imaging techniques include positron emission tomography (PET) [5; 6; 7; 8], single-photon emissioncomputed tomography (SPECT) [9; 10], MRI with contrast agent enhancement (such as magnetic nanoparticles) [11; 12; 13; 14; 15], optical/fluorescence imaging [14; 16; 17], and photoacoustic imaging (PAI) [18; 19; 20]. PET and SPECT involve ionization radiation with the long half-life of radiotracers which limits the temporal resolution. In addition, they both have relatively low spatial resolution in localizing the tumors. The relatively slow data acquisition time of MRI often generates motion artifact issue and a reduced signal-to-noise ratio [21]. In optical imaging, fluorescent dyes, quantum dots, or nanoparticles conjugated to targeted antibodies or peptides are commonly used as contrast agents. Optical molecular imaging has a relatively high spatiotemporal resolution without ionization radiation. However, the limited tissue penetration capability of light prevents the use of optical techniques for noninvasive imaging of deeply located organs like the pancreas.  
PAI is an emerging biomedical imaging technique that combines the optical contrast with an increased ratio of imaging depth to spatial resolution capable of providing anatomical, functional, molecular properties of biological tissue with a high resolution [22; 23; 24; 25; 26; 27; 28; 29; 30; 31; 32]. In PAI, images are formed through detecting pulsed laser-induced wideband acoustic waves. The image contrast in PAI originates from light absorption in tissue. Similar to optical imaging, PAI also suffers from the penetration limitation, and cannot be used to noninvasively image deeply located organs such as the pancreas.  
Multifunctional iron oxide nanoparticles (IONPs) have been developed for targeted molecular imaging and drug delivery with their capabilities of tumor targeting, imaging, and delivery of therapeutic agents. IONPs have been widely used to enhance the image contrast for magnetic resonance imaging (MRI) and fluorescence imaging in animals [14; 33; 34].  
The goal of this study is to demonstrate a multimodal endoscopic approach combined with targeted multifunctional IONPs for the molecular imaging of pancreatic tumors, where the pancreas can be directly accessed with minimal invasiveness using a 1 mm-diameter miniature endoscope coupled with a novel fan-shaped two-dimensional (2D) scanning mechanism.