TY - JOUR T1 - Development and Testing of an Integrated Catheter for Beta Detection and Intramyocardial Therapeutic Delivery JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1949 LP - 1949 VL - 57 IS - supplement 2 AU - John Stendahl AU - Eliahoo Nataneli AU - Marialisa Stagliano AU - Milica Vukmirovic AU - Francesco d'Errico AU - Albert Sinusas AU - Farhad Daghighian Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/1949.abstract N2 - 1949Objectives We have set out to design an integrated theranostic system that utilizes molecularly-targeted radiotracers to achieve localized intramyocardial therapeutic delivery. Our goal is to create a steerable endovascular catheter-based device that: a) identifies injured myocardium via endocardial detection of systemically delivered beta-emitting radiotracers, and b) utilizes the molecular signal to guide delivery of therapeutics to the injured tissue via direct intramyocardial injection. Current experimental procedures are exploring delivery of therapeutics such as stem cells, anti-inflammatory agents, and genetic material to specific locations in the heart via fluoroscopy or an electromagnetic field with electromechanical mapping. We hypothesize that molecularly-guided intramyocardial delivery of therapeutics will maximize therapeutic benefits to injured myocardium and minimize systemic side effects.Methods The prototype theranostic catheter developed for both radiation detection and molecularly-targeted therapeutic injection is shown in Fig. A. The diameter of the flexible catheter is 2.4 mm. The detector on the catheter tip consists of a plastic scintillator (BC-412, St. Gaugin, Fr) coupled to a 1 mm x 1 mm solid state photodiode (Hamamatsu Photonics, Japan). The plastic scintillator was selected for its high efficiency detection of positrons and minimal sensitivity to gamma rays, which reduces signals from background radiation and increases spatial resolution. The catheter tip also features a retractable 25 G needle for therapeutic delivery, which can be accessed via an injection port on the catheter base. Basic feasibility experiments were conducted to assess the prototype device’s sensitivity and ability to measure signals from intramyocardial beta-emitting radiotracers. Briefly, 50 μL quantities of serially diluted aqueous 18FDG were injected locally into sections of an ex vivo pig heart at depths of 1 mm from the endocardial surface. 18FDG signals were assessed by collecting counts with the catheter tip in direct endocardial contact.Results Catheter-based endocardial measurements of 18FDG injected intramyocardially in biologically-relevant activities at depths of 1 mm are shown in Fig. B. The prototype catheter device demonstrates a concentration-dependent relation to signal strength, recording values of 2 and 21 counts per second (CPS) for the 1 and 10 μCi samples, respectively. The sensitivity of the detector was 3000 CPS/μCi when in direct contact with a 1 mm2 source of 18FDG. The difference in magnitude of signals detected in direct contact and in tissue (1 mm deep injections) reflects the limited range of 18F positrons in tissue (Rmax = 2.4 mm). This contributes to high spatial resolution radiotracer detection to guide therapeutic delivery.Conclusions The prototype theranostic device features a flexible, narrow gauge catheter with a retractable needle and a solid state beta detector capable of high sensitivity endocardial measurement. This hybrid catheter-based system can be delivered percutaneously to detect molecularly-targeted radiotracer signals on the endocardial surface and direct intramyocardial delivery of therapeutics to maximize benefit. One potential application of this technology is the delivery of therapeutics (e.g. stem cells) to injured myocardium following infarction. In vivo experiments are planned to further test and improve this novel device and method. $$graphic_13DED0AD-0433-4B42-8C6B-7E943DC64E43$$ ER -