Current Molecular Imaging (Discontinued) - Volume 4, Issue 1, 2015

The use of 2-deoxy-2-[18F] fluoro-D-glucose (FDG) and positron emission tomography/ computed tomography (PET/CT) is increasing rapidly – and the list of emerging and evolving applications is everexpanding in a multitude of clinical settings. In this anniversary review celebrating four decades of FDG, we will outline an overview of the present status of FDG imaging with emphasis on clinical implementation in the main indications of FDG-PET/CT, i.e. neurology and psychiatry, oncology, cardiovascular diseases, and infectious and inflammatory diseases, including some general considerations towards clinical benefit and potential future directions.

Background: Tc-99m labeled Glucaric Acid (Tc-GA) and In-111 labeled human fibrinogen (In-HF) were used to demonstrate reduction in myocardial infarction and microvascular injury in rabbit preconditioned ischemic hearts. Methods: New Zealand White rabbits were subjected to preconditioning or non-preconditioning ischemic myocardial injury. Reperfusion was established after 45 min of circumflex occlusion and then Tc-GA and In-HF were injected intravenously. Anteroposterior gamma images were acquired for 4 hours. Perfusion defects, histochemical infarct size and radiotracer uptake were determined. Results: In vivo and ex vivo images were consistent with the gamma scintillation counting data. Minimal GA and fibrin depositions were seen in preconditioned ischemic hearts (3.78± 10.7 and 0 % of total myocardial area respectively) whereas the areas delineated by GA and fibrin deposition in non-ischemic preconditioned hearts were larger (61.9± 34.5 and 60.0± 32.7%). Infarct size of preconditioned ischemic hearts was 4.6±1.9 % of the left ventricle, whereas that of non-preconditioned ischemic hearts was 24.1±5.9% (P <0.01) assessed by histochemical technique. Infarct size from imaging was approximately 2.5 times that of the histochemical assessment. The regions of perfusion defect were similar (23.3±4.1 vs 26.5+8.5% respectively). Images of Tc-GA uptake and In-HF deposition were consistent with histochemical and radiotracer uptake data indicating minimal myocardial injury in preconditioned ischemic hearts even though areas of perfusion defect were similar. Conclusion: The data indicates that ischemic precondition not only preserved myocyte viability but also reduced microvascular injury.

A protocol to load perfluoro-crown-ether (PFCE) nanoemulsion directly into yeast-derived glucan particles (GPs) was developed. It was observed that the PFCE encapsulation did not affect the 19F-MRI properties of the nanoemulsion that is currently in clinical trials. GPs loaded with PFCE nanoemulsion were taken up avidly by murine macrophages in vitro, resulting in a cellular uptake 150 % higher than the not GPs-entrapped nanoemulsion. Accordingly, a corresponding improvement in the 19F-MRI detection of the labelled cells can be obtained. The high biotolerability and versatility of GPs, make these microcarriers a promising option for designing of improved in vivo cellular imaging protocols.

Purpose: The unambiguous prostate cancer diagnosis is of high global interest. Magnetic Resonance Imaging (MRI) is a low invasive modality in early stages of tumor diagnosis, especially for cancer detection. The study aim is to synthesize Gd3+ based silica mesoporous nanosphere conjugated with Monoclonal Antibody (Mab C595) and evaluate its ability as nanoprobe for prostate cancer cells detection. Method: Here, a nanoprobe, specifically recognizing in vivo MUC-1 antigen in prostate cancer cells, was synthesized and evaluated. The in vitro studies included cell toxicity, cell binding and immune reactivity assay. MR imaging parameters of this nanoprobe were investigated by MRI. Results: Results showed that this nanoprobe is a selective MUC-1 detector, without any significant cell toxicity. Conclusion: This study confirmed that this nanoprobe is potentially a selective prostate molecular imaging agent for cancer cell detection.

Cocaine has been known to inhibit dopaminergic and serotonergic systems. Here, we aimed to study the addictive effects of cocaine on both systems of rats after chronic treatments. Rats were treated with vehicle or cocaine for four months, and the changes of behavior and expressions and activity of dopaminergic and serotonergic systems were assessed. Locomotion was used to estimate the animal behavior. The neuronal imaging of dopamine D2 receptor (D2R) with [11C]raclo- [11C]raclopride/microPET and serotonin transporter (SERT) with [123I]-2-((2-((dimethylamino) methyl) phenyl) thio)-5- iodophenylamine ([123I]ADAM)/gamma scintigraphy was performed for determining the specific striatum/midbrain binding ratios. Animal Magnetic Resonance Imaging (MRI) and immunohistochemistry (IHC) were applied to assess the anatomical changes in the rat brains. The activated locomotion was found for the first ten weeks, and gradually recovered to the baseline. Brain D2R imaging (i.e., [11C]raclopride/microPET) showed the decreased ratio of striatum/midbrain during the study and two weeks post the withdrawal of cocaine treatments. Brain SERT imaging (i.e., [123I]ADAM/gamma scintigraphy) was also found similar to the declined ratio of midbrain/cerebellum. However, animal MRI did not find brain hemorrhage and edema. Notably, the results obtained from IHC showed serious neuronal damage with decreased Tyrosine Hydroxylase (TH)-positive and increased glial fibrillary acidic protein (GFAP)-positive expressions in the critical brain regions. These results demonstrate that the predominant effect of chronic cocaine treatments on the dopaminergic system is more severe than on the serotonergic system as evaluated with the behavioral tolerance, D2R impairment, and dopamine neuron deficit.

Translational projects frequently test agents by intravenous injection into small animals. One problem is that it is usually uncertain exactly how successful each injection is at time of administration. This leads to high variation in measurements and necessitates the use of larger groups of animals. To circumvent this problem, we introduce a novel near infrared imaging method to determine injection success in adult and neonatal mice. By co-injecting a near infrared fluorophore AngioSense 750 with a therapeutic agent, the location of near infrared fluorescence can be used to determine injection quality. To test this method, an Adenoviral (Ad) vector expressing luciferase was co-injected with AngioSense at different sites in adult and neonatal mice. When injection was successful, the near infrared fluorophore entered into the bloodstream and spread throughout the body of the animal and vector-mediated luciferase activity was observed in the liver. When intravenous injection was a failure, the near infrared and subsequent luciferase signals remained localized at the injection site. This work has been performed with adult and neonatal mice using an adenoviral vector, but it can be translated to other small animals or small anatomic sites for any therapeutic or basic science application.

Background: Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder in response to a major traumatic event. Higher levels of trauma may be associated with more deficits in the brain SERT availability. We investigated the in vivo dynamitic change of SERT availability in the brain of PTSD rat with increasing severity of disease with 4-[18F] ADAM PET which reflects the SERT availability. Methods: Pavlovian fear conditioning model of PTSD was used in this study. Sprague-Dawley rats (N=6/group) were conditioned with 3, 6 and 10 tone-shock pairings at 1 min intervals, and the freezing responses was measured as the percentage of time spent in freezing during 1 min interval. Static PET imaging was performed in PTSD animals after administration of 2-(2-amino-4-[18F] -fluorophenylthio) benzylamine (4-[18F]-ADAM) (150 µCi/100µl, i.v.). One day later, the brains were removed and grounded for the quantitation of AMPA receptor trafficking. Results: The conditioned 6 or 10 tone-shock pairings exhibited higher level of cue-evoked freezing behavior compared with 3 tone-shock pairings groups (p< 0.01). PET results showed that a positive correlations between SERT availability in the brain regions including amygdala, caudate/putamen, hippocampus, hypothalamus, midbrain, pituitary, frontal cortex and cerebellum in the groups of mild or moderate PTSD but a negative correlation in the severe group. The phosphorylation of GluR1 at Ser831 which were subunits of AMPA was dramatically increased in the amygdala and hippocampus of severe group compared with control group. Conclusions: The results support that 4-[18F]-ADAM PET could be used to monitor the alteration of SERT availability associated with PTSD severity.