Small-animal PET refers to imaging of animals such as rats and mice using dedicated PET scanners. Small-animal PET has been used extensively in modern biomedical research. It provides a quantitative measure of the 3-dimensional distribution of a radiopharmaceutical administered to a live subject noninvasively. In this article, we will discuss the operational and technical aspects of small-animal PET; make some comparisons between small-animal PET and human PET systems; identify the challenges of, opportunities for, and ultimate limitations in applying small-animal PET; and discuss some representative small-animal PET applications. Education objectives: After reading this article, the technologist will be able to explain the requirements and benefits of small-animal PET in biomedical research, describe the design and general characteristics of a small-animal PET system, list and describe some of the challenges of imaging small animals, and discuss several small-animal PET applications.

Rat brain images acquired with a small animal positron emission tomography (PET) camera and reconstructed with the three-dimensional (3-D) ordered-subsets expectation-maximization (OSEM) algorithm with resolution recovery have better quality when the brain is imaged by itself than when inside the head with surrounding background activity. The purpose of this study was to characterize the dependence of this effect on the level of background activity, attenuation, and scatter. Monte Carlo simulations of the imaging system were performed. The coefficient of variation from replicate images, full-width at half-maximum (FWHM) from point sources and image profile fitting, and image contrast and uniformity were used to evaluate algorithm performance. A rat head with the typical levels of five and ten times the brain activity in the surrounding background requires additional iterations to achieve the same resolution as the brain-only case at a cost of 24% and 64% additional noise, respectively. For the same phantoms, object scatter reduced contrast by 3%-5%. However, attenuation degraded resolution by 0.2 mm and was responsible for up to 12% nonuniformity in the brain images suggesting that attenuation correction is useful. Given the effects of emission and attenuation distribution on both resolution and noise, simulations or phantom studies should be used for each imaging situation to select the appropriate number of OSEM iterations to achieve the desired resolution-noise levels.

Conventional single photon emission computed tomography (SPECT) relies on mechanical collimation whose resolution and sensitivity are interdependent, the best performance a SPECT system can attain is only a compromise of these two equally desired properties. To simultaneously achieve high resolution and sensitivity, we propose to use sensitive detectors constructed in a m ulti-l a yer in t e r spaced mosa ic d e tector s (MATRICES) architecture to accomplish part of the collimation needed. We name this new approach self-collimation. We evaluate three self-collimating SPECT systems and report their imaging performance: 1) A simulated human brain SPECT achieves 3.88% sensitivity, it clearly resolves 0.5-mm and 1.0-mm hot-rod patterns at noise-free and realistic count-levels, respectively; 2) a simulated mouse SPECT achieves 1.25% sensitivity, it clearly resolves 50- $\mu \text{m}$ and 100- $\mu \text{m}$ hot-rod patterns at noise-free and realistic count-levels, respectively; 3) a SPECT prototype achieves 0.14% sensitivity and clearly separates 0.3-mm-diameter point sources of which the center-to-center neighbor distance is also 0.3 mm. Simulated contrast phantom studies show excellent resolution and signal-to-noise performance. The unprecedented system performance demonstrated by these 3 SPECT scanners is a clear manifestation of the superiority of the self-collimating approach over conventional mechanical collimation. It represents a potential paradigm shift in SPECT technology development.

This work is part of a feasibility study to develop SPECT imaging capability on a lutetium oxyorthosilicate (LSO) based animal PET system. The SPECT acquisition was enabled by inserting a collimator assembly inside the detector ring and acquiring data in singles mode. The same LSO detectors were used for both PET and SPECT imaging. The intrinsic radioactivity of (176)Lu in the LSO crystals, however, contaminates the SPECT data, and can generate image artifacts and introduce quantification error. The objectives of this study were to evaluate the effectiveness of a LSO background subtraction method, and to estimate the minimal detectable target activity (MDTA) of image object for SPECT imaging. For LSO background correction, the LSO contribution in an image study was estimated based on a pre-measured long LSO background scan and subtracted prior to the image reconstruction. The MDTA was estimated in two ways. The empirical MDTA (eMDTA) was estimated from screening the tomographic images at different activity levels. The calculated MDTA (cMDTA) was estimated from using a formula based on applying a modified Currie equation on an average projection dataset. Two simulated and two experimental phantoms with different object activity distributions and levels were used in this study. The results showed that LSO background adds concentric ring artifacts to the reconstructed image, and the simple subtraction method can effectively remove these artifacts-the effect of the correction was more visible when the object activity level was near or above the eMDTA. For the four phantoms studied, the cMDTA was consistently about five times of the corresponding eMDTA. In summary, we implemented a simple LSO background subtraction method and demonstrated its effectiveness. The projection-based calculation formula yielded MDTA results that closely correlate with that obtained empirically and may have predicative value for imaging applications.

In this report we demonstrate the outstanding advantages of multifunctional nanoplatforms for cancer-imaging and therapy. The non-toxic polyacrylamide (PAA) nanoparticles (size:18-25 nm) formulation drastically changed the pharmacokinetic profile of the ¹²⁴I- labeled chlorophyll-a derivative (formulated in 10% ethanol in PBS) with a remarkable enhancement in tumor uptake, and significantly reduced uptake in spleen and liver. Among the various nanoformulations investigated, the ¹²⁴I- labeled photosensitizer (dose: 0.6142 MBq), and the cyanine dye-nanoparticles (CD-NP) conjugate (dose 0.3 μmol/kg) in combination showed great potential for tumor imaging (PET/NIR fluorescence) in BALB/c mice bearing Colon26 tumors. Compared to free non-labeled photosensitizer, the corresponding PAA nanoformulation under similar treatment parameters showed a remarkable enhancement in long-term tumor cure by PDT (photodynamic therapy) and provides an opportunity to develop a single nanoplatform for tumor-imaging (PET/fluorescence) and phototherapy, a practical “See and Treat” approach.