Purpose: Positron emission tomography (PET) is a useful imaging modality that quantifies the physiological distributions of radiolabeled tracers in vivo in humans and animals. However, this technique is unsuitable for multiple-tracer imaging because the annihilation photons used for PET imaging have a fixed energy regardless of the selection of the radionuclide tracer. This study developed a multiisotope PET (MI-PET) system and evaluated its imaging performance. Methods: Our MI-PET system is composed of a PET system and additional c-ray detectors. The PET system consists of pixelized gadolinium orthosilicate (GSO) scintillation detectors and has a ring geometry that is 95 mm in diameter with an axial field of view of 37.5 mm. The additional detectors are eight bismuth germanium oxide (BGO) scintillation detectors, each of which is 50 9 50 9 30 mm 3 , arranged into two rings mounted on each side of the PET ring with a 92-mminner diameter. This system can distinguish between different tracers using the additional c-ray detectors to observe prompt c-rays, which are emitted after positron emission and have an energy intrinsic to each radionuclide. Our system can simultaneously acquire double-(two annihilation photons) and triple-(two annihilation photons and a prompt c-ray) coincidence events. The system's efficiency for detecting prompt de-excitation c-rays was measured using a positron-c emitter, 22 Na. Dual-radionuclide ( 18 F and 22 Na) imaging of a rod phantom and a mouse was performed to demonstrate the performance of the developed system. Our system's basic performance was evaluated by reconstructing two images, one containing both tracers and the other containing just the second tracer, from list-mode data sets that were categorized by the presence or absence of the prompt c-ray. Results: The maximum detection efficiency for 1275 keV c-rays emitted from 22 Na was approximately 7% at the scanner's center, and the minimum detection efficiency was 5.1% at the edge of the field of view. Dual-radionuclide imaging of the point sources and rod phantom revealed that our system maintained PET's intrinsic spatial resolution and quantitative nature for the second tracer. We also successfully acquired simultaneous double-and triple-coincidence events from a mouse containing 18 F-fluoro-deoxyglucose and 22 Na dissolved in water. The dual-tracer distributions in the mouse obtained by our MI-PET were reasonable from the viewpoints of physiology and pharmacokinetics. Conclusions: This study demonstrates the feasibility of multiple-tracer imaging using PET with additional c-ray detectors. This method holds promise for enabling the reconstruction of quantitative multiple-tracer images and could be very useful for analyzing multiple-molecular dynamics.

We developed a positron emission tomography (PET) system for multiple-isotope imaging. Our PET system, named multiple-isotope PET (MI-PET), can distinguish between different tracer nuclides using coincidence measurement of prompt γ-rays, which are emitted after positron emission. In MI-PET imaging with a pure positron emitter and prompt-γ emitter, because of the imperfectness of prompt γ-ray detection, an image for a pure positron emitter taken by MI-PET is superposed by a positron-γ emitter. Therefore, in order to make isolated images of the pure positron emitter, we developed image reconstruction methods based on data subtraction specific to MI-PET. We tested two methods, subtraction between reconstructed images and subtraction between sinogram data. In both methods, normalization for position dependence of the prompt γ-ray sensitivity is required in addition to detector sensitivity normalization. For these normalizations, we performed normalization scans using cylindrical phantoms of the positron-γ emitters 44m Sc (prompt γ-ray energy: 1157 keV) and 22 Na (prompt γray energy: 1274 keV). A long period measurement using the activity decay of 44m Sc (T1/2 = 58.6 hours) elucidated that the acquisition ratio between the prompt γ-rays coincided with PET event and pure PET event changes on the basis of object activities. Therefore, we developed a correction method that involves subtraction parameters dependent on the activities, i.e., the counting rate. We determined that correction for sensitivity normalization in variation of activity can be performed using only the triple-coincidence rate as an index, even if using a different nuclide from that used for normalization. From analysis of dual-tracer phantom images using 18 F and 44m Sc or 18 F and 22 Na, data subtraction in the sinogram data with sensitivity correction gives a higher quality of isolated images for the pure positron emitter than those from image subtractions. Furthermore, from dual-isotope ( 18 F-FDG and 44m Sc) mouse imaging, we concluded that our developed method can be used for practical imaging of a living organism.