With a half-live of 4.2 days, Iodine-124 (124I) is suitable for studying antibodies and drug analogues in animals that have a biological half-live in days. The special challenges with 124I imaging on animal PET are: 1) the high fraction of high-energy, non-annihilation gamma-rays that introduce true coincidences which elevate the image background activity, and 2) the significant degradation of spatial resolution due to the high positron energies. By simulations and experiments on an animal PET scanner, we characterized these two unique degradation factors and evaluated the corresponding correction methods. The preliminary results of applying non-annihilation true coincidence correction and using 124I specific point spread function in the system matrix of reconstruction algorithm showed improved contrast and resolution recovery. These findings indicate that higher-resolution, quantitative 124I applications can be achieved.