Abstract--Radiolabeled agents that bind to specific receptors have shown great promise in diagnosing and characterizing tumor cell biology. A second area of interest is in vivo imaging of gene transcription and protein expression. The radioisotope I 125 is commercially available as a label for molecular probes and utilized by researchers in small animal studies. We propose an advanced imaging detector based on planar NaI(Tl) integral assembly with a Hamamatsu Flat Panel PMT, representing one of the best trade-off between spatial resolution and detection efficiency. We tested the in-vivo performance of the detector by acquiring images of mice as a part of a study of inflammatory bowel disease (IBD). In this study, four 25g mice with an IBD-like phenotype (SAMP1/YitFc) were injected with 375, 125, 60 and 30 μCi of 125 I-labelled antibody against MAdCAM-1, a gut-specific endothelial cell adhesion molecule that is up-regulated in the presence of inflammation. Two mice without bowel inflammation were injected with 150 and 60 μCi of the labelled anti-MAdCAM- 1 antibody as controls. To better evaluate the performances of the integral assembly detector, we also acquired mice images with a dual modality ( X and Gamma Ray) camera dedicated for small animal imaging. The results of this new detector are impressive: images of SAMP1/YitFc injected with 30 μCi activity show inflammation throughout the intestinal tract, with the disease very well defined at two hours post-injection. I. INTRODUCTION adiolabeled agents that bind to specific receptors have shown great promise in selectively targeting, diagnosing and characterizing tumor cell biology. A second area with wide applications is in vivo imaging of gene transcription and protein expression. The radioisotope I 125 is readily available commercially as a label for molecular biology probes that are of interest for researchers in small animal imaging. Iodine125 Manuscript received October,21, 2004. Maria Nerina Cinti is with Biophysics PhD School, University of Rome La Sapienza - P.le A. Moro 6 – 00161 Rome - Italy (telephone:+39-06-49918277, e-mail: marianerina.cinti @uniroma1.it). Majewki S., Popov V. and Welch B.L are with Thomas Jefferson National Facility, Newport News, VA-USA Williams M.B., Bachmann C., Cominelli F, Kundu B.K. and Stolin.A. are with Department of Radiology, University of Virginia, Charlottesville,VA,USA Roberto Pani, Devincentis G. and Betti M. are with Department of Experimental Medicine and Patology - University of Rome La Sapienza- 00166 Rome-Italy. is used to label a wide range of molecules like nucleic acids, antibodies, ligands etc. Moreover its half life of 60.2 days makes it attractive for long time in vivo experiment. An important advantage of iodine imaging is that iodine-labeled molecules provide a convenient bridge from animal models to humans. One can replace I 125 by I 123 (13.2 h half-life), whose 159-keV gamma rays have a sufficiently long path-length for imaging in humans. As is typical in nuclear medicine, the ideal detector would be the best trade-off between spatial resolution, detection sensitivity, detection area, and cost effectiveness. Unfortunately, the low energy emissions of I 125 make it difficult to satisfy both requirements of very high intrinsic spatial resolution and large detection area. Also, due to the low I 125 radioactivity administered to mice, signal attenuation associated with use of a very high spatial resolution parallel collimator could hamper the formation of a readable image. Other authors have been utilizing scintillation arrays, but unfortunately the present technology of scintillation arrays made by CsI(Tl) or NaI(Tl) materials limits the pixel size down to 1.0-1.2 mm with a dead zone of about 0.2 mm [1,2]. Such a dead zone needs to optically insulate each individual crystal, strongly reducing the detection efficiency. In addition, the low light output relative to the low X-ray energies emitted from I 125 impairs the pixel identification with an operative reduction of spatial resolution (around 2 mm) and contrast of the imaging system. On the other side, the employment of NaI(Tl) planar detectors limited intrinsic spatial resolution to 3.1 mm.[3] In this paper we present a more advanced imaging detector based on 1.5 mm planar NaI(Tl) integral assembly with a Hamamatsu H8500 flat panel PSPMT representing one of the best trade-offs between spatial resolution and detection efficiency, with an useful detection area of about 50x50 mm 2 . The detector was produced by Bicron. Calibration measurements were performed with collimated radioactive sources and by capillaries filled with Tc 99m and I 125 liquid sources. We tested in-vivo imaging performance of the detector by acquiring images of mice, injected with an I 125 labeled antibody, as a part of a study of inflammatory bowel disease (IBD). Iodine 125 imaging in mice using NaI(Tl)/Flat panel PMT integral assembly Cinti M.N., IEEE member, Majewski S., IEEE member, Williams M.B., Bachmann C., Cominelli F., Kundu B.K., Stolin.A., Popov V., Welch B.L., DeVincentis G., Betti M. and Pani R., IEEE member. R 0-7803-8701-5/04/$20.00 (C) 2004 IEEE