Systems and methods are provided for a catheter-based system of image-guided internally-administered treatment of medical conditions such as, for example, pancreatic cancer. A distal end of a catheter is positioned at a target site inside a patient's body. An imaging probe extended through the catheter collects image data of patient tissue at the target site. The image data is processed and a treatment plan is developed. A radiation source positioned at the distal end of the catheter without removing the catheter. In this way, images collected at the target tissue site can be used to develop a treatment plan and to guide the localized positioning and operation of a treatment device at the same internal tissue site—thereby providing higher resolution imaging than external-based imaging modalities and reduced exposure to radiation as compared to externally applied radiation therapies.