Fig 1.
Characterization of FDG labeling of human erythrocytes.
(A) FDG uptake by 5 day old and 1 day old human erythrocytes.The relative percent FDG uptake by 5 days old human erythrocytes (post-phlebotomy) vs.1 day old human erythrocytes. Either 250 μl of 1 day old human erythrocytes or 5 day old erythrocytes were incubated with 100 μl (≈ 37MBq) 18F-FDG for 2 hours at 37° C. (B) Human erythrocyte uptake of FDG after 30 minute incubation approaches that of 2 hour incubation. 250 μl of 1 day old human erythrocytes were incubated with 100 μl (≈ 37MBq) FDG at 37° C for 30 minutes, 1 hour, and 2 hours. Sample number = 3/timepoint. (C) Relative % free FDG remaining in the FDG-labeled erythrocyte fraction (250 μl), original incubation supernatant, and wash supernatants. (D) Slow gradual release of intracellular FDG over time (R2 = 0.9586; sample number = 3/timepoint) (S1 File).
Fig 2.
Minimal erythrocyte membrane damage is seen after repeated centrifugation and wash steps of cell labeling technique.
(A) Unperturbed (negative) control group. (B) Mock FDG labeled cell group. (C) CaCl2-treated group. Each figure is representative of 3 samples per group.
Fig 3.
Whole body microPET images of control FDG injected mouse and mouse injected with FDG-labeled human erythrocytes.
(A) Whole body PET image of a control splenectomized NSG mouse injected with 1.7 MBq of free FDG. 3(B) Whole body ECG-gated PET image of a splenectomized NSG mouse injected with 10.4 MBq of 18F-FDG-labeled human erythrocytes. Number of mice in FDG-erythrocyte injected mouse group = 4.
Fig 4.
Fused PET/CT images of thorax of control FDG injected mouse and mouse injected with FDG-labeled human erythrocytes.
(A) Axial (left), coronal (middle), and sagittal (right) fused microPET/CT images of the mouse thorax show intense physiologic FDG uptake by the myocardium of the left ventricle in a splenectomized NSG mouse injected with 2.2 MBq of free FDG. Green circle indicates lumen of the left ventricle. (B) Axial (left), coronal (middle), and sagittal (right) fused microPET/CT images of the mouse thorax show FDG activity within the lumen of the cardiac chambers (green circles) in a splenectomized NSG mouse injected with 1.7 MBq of FDG-labeled human erythrocytes. Pulmonary perfusion about the heart is also visualized.
Fig 5.
Time activity curve of mouse injected with FDG-labeled human erythrocytes.
TAC of the heart of a mouse injected with FDG-labeled erythrocytes shows expected blood pool activity of FDG-labeled human erythrocytes with immediately high FDG activity (≤1 minute) followed by a small initial decline (4–14 minutes) and then activity plateau (14–30 minutes).
Fig 6.
MicroPET images of the mouse head and neck allow visualization of major head and neck vessels.
Major vessels in the neck of the mice injected with FDG-labeled erythrocytes could be visualized, such as the external jugular veins in the lateral neck (yellow arrows), the smaller common carotid arteries in the central neck (red arrows), and the circle of Willis (blue arrows).
Fig 7.
Comparison of calculated human organ dose from FDG-labeled erythrocytes with intravenous (IV) FDG.
Organ dose estimates from FDG-labeled erythrocytes were calculated under conditions of 100% in vivo FDG retention and decay (FDG RBCs Ideal), and after 25% FDG excretion (FDG RBCs 25% free). In addition, organ dose estimates for intravenous FDG injection (FDG IV Ideal) were also calculated for comparison purposes.
Table 1.
Calculated organ absorbed doses using the OLINDA dosimetry software and Christy-Eckerman phantom.