Optimization of [(11)C]raclopride positron emission tomographic rat studies: comparison of methods for image quantification.

The goal of this study was to compare different quantification approaches and reconstruction methods to estimate the binding potential in [11C]raclopride studies in rats. The final aim was to determine if the results obtained with short-acquisition scanning were comparable to the results obtained with long-acquistion (conventional) scanning. We analyzed two rat data sets: a baseline versus a pretreatment study (with cold raclopride) and a young versus an old animal group comparison. The study results support the contention that optimization of [11C]raclopride positron emission tomographic studies in rats by shortening the acquisition time is feasible. In addition, filtered backprojection is recommended as a reconstruction algorithm, although iterative methods may be more sensitive to detect within-group differences.

Erythrocytes labeled with [(18) F]SFB as an alternative to radioactive CO for quantification of blood volume with PET.

Inhaled radioactive CO is currently the tracer of choice for blood volume quantification by positron emission tomography (PET). This measurement is of great interest for several clinical and research applications. However, owing to the short half-life of the radiolabeled CO, it can only be used in centers equipped with a cyclotron. In the present work, we propose an alternative method to label the red blood cells with [(18) F] in order to obtain blood volume measurements by PET. The use of the radioactive synthon [(18) F] N-succinimidyl 4-[(18) F]fluorobenzoate ([(18) F]SFB) was evaluated for erythrocyte labeling and PET blood volume imaging. The images provided by [(18) F]SFB labeled erythrocytes were compared with those obtained with inhaled [(11) C]CO. Blood volumes obtained with [(18) F]SFB labeled erythrocytes were similar to those obtained with [(11) C]CO in all of the evaluated organs with the exception of spleen, which presented lower uptake with this method. Since the [(18) F]-SFB binds irreversibly to red blood cells, in vivo stability of the radiolabel was higher compared with the [(11) C]CO method. Additionally, owing to the longer half-life and the shorter positron range of [(18) F], the image quality was also higher with the [(18) F]SFB radiolabeled erythrocytes. The labeling of red blood with [(18) F]SFB represents an advantageous alternative to radioactive CO for blood volume measurement by PET and cardiovascular isotopic imaging.

In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography.

Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [(18)F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [(11)C]-PIB (Pittsburg compound B) have shown exceptional value in animal models and AD patients. Previously, the glucose analogue [(18)F]-FDG (2-[(18)F]fluorodeoxyglucose) allowed researchers and clinicians to evaluate the brain glucose consumption and proved its utility for the early diagnosis and the monitoring of the progression of AD. Animal models of AD are based on the transgenic expression of different human mutant genes linked to familial AD. The novel transgenic 5XFAD mouse containing 5 mutated genes in its genome has been proposed as an AD model with rapid and massive cerebral amyloid deposition. PET studies performed with animal-dedicated scanners indicate that PET with amyloid-targeted radiotracers can detect the pathological amyloid deposition in transgenic mice and rats. However, in other studies no differences were found between transgenic mice and their wild type littermates. We sought to investigate in 5XFAD mice if the radiotracers [(11)C]-PIB, and [(18)F]-Florbetapir could quantify the amyloid deposition in vivo and if [(18)F]-FDG could do so with regard to glucose consumption. We found that 5XFAD animals presented higher cerebral binding of [(18)F]-Florbetapir, [(11)C]-PIB, and [(18)F]-FDG. These results support the use of amyloid PET radiotracers for the evaluation of AD animal models. Probably, the increased uptake observed with [(18)F]-FDG is a consequence of glial activation that occurs in 5XFAD mice.

Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia.

PURPOSE: [¹8F]Fluoromisonidazole (¹8F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of ¹8F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes. PROCEDURES: Rats (n = 14) were subjected to permanent ischemia by intraluminal occlusion of the middle cerebral artery in order to assess by PET the uptake of ¹8F-FMISO at various times over 24 h following ischemia. The PET results were compared to histological changes with Nissl and 2,3,5 triphenyltetrazolium chloride staining. RESULTS: Elevated uptake of ¹8F-FMISO was detected in the infarcted area up to 8 h after occlusion but was no longer detected at 24 h, a time point coincident with pan necrosis of the tissue. CONCLUSIONS: Our findings suggest that salvageable tissue persists for up to 8 h in this rat model of brain ischemia. We propose ¹8F-FMISO PET as a tool for evaluating the ischemic penumbra after cerebral ischemia.