Serotonin 5HT2 Receptor Imaging in the Human Brain Using Positron Emission Tomography and a New Radioligand, [18F]Altanserin: Results in Young Normal Controls

Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376–1,680 mCi/μmol) [18F]altanserin. Arterial blood samples were obtained and the plasma time–activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential ( Bmax/ KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans.

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In vivo Muscarinic Cholingeric Receptor Imaging in Human Brain with [11C]Scopolamine and Positron Emission Tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.18 ◽

1992 ◽

Vol 12 (1) ◽

pp. 147-154 ◽

Cited By ~ 75

Author(s):

K. A. Frey ◽

R. A. Koeppe ◽

G. K. Mulholland ◽

D. Jewett ◽

R. Hichwa ◽

...

Keyword(s):

Positron Emission Tomography ◽

Kinetic Analysis ◽

Muscarinic Receptor ◽

Emission Tomography ◽

In Vivo Studies ◽

Receptor Imaging ◽

Arterial Blood ◽

Positron Emission

Cerebral muscarinic cholinergic receptors were imaged and regionally quantified in vivo in humans with the use of [11C]scopolamine and positron emission tomography. Previous studies in experimental animals have suggested the utility of radiolabeled scopolamine for in vivo measurements, on the bases of its maintained pharmacologic specificity following systemic administration and the exclusion of labeled metabolites from the brain. The present studies describe the cerebral distribution kinetics of [11C]scopolamine in normal subjects following intravenous injection. Scopolamine is initially delivered to brain in a perfusion-directed pattern. After 30 to 60 min, activity is lost preferentially from cerebral structures with low muscarinic receptor density including the cerebellum and thalamus. Activity continues to accumulate throughout a 2 h postinjection period in receptor-rich areas including cerebral cortex and the basal ganglia. The late regional concentration of [11C]scopolamine does not, however, accurately parallel known differences in muscarinic receptor numbers in these receptor-rich areas. Tracer kinetic analysis of the data, performed on the basis of a three-compartment model, provides receptor binding estimates in good agreement with prior in vitro measurements. Kinetic analysis confirms significant contributions of ligand delivery and extraction to the late distribution of [11C]scopolamine, reconciling the discrepancy between receptor levels and tracer concentration. Finally, a novel dual-isotope method for rapid chromatographic processing of arterial blood samples in radiotracer studies is presented. The combination of rapid chromatography and compartmental analysis of tracer distribution should have broad utility in future in vivo studies with short-lived radioligands.

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Rapid Feasibility Studies of Tracers for Positron Emission Tomography: High-Resolution PET in Small Animals with Kinetic Analysis

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1991.157 ◽

1991 ◽

Vol 11 (6) ◽

pp. 926-931 ◽

Cited By ~ 52

Author(s):

M. Ingvar ◽

L. Eriksson ◽

G. A. Rogers ◽

S. Stone-Elander ◽

L. Widén

Keyword(s):

Positron Emission Tomography ◽

Emission Tomography ◽

Whole Body ◽

Small Animals ◽

Pharmacological Properties ◽

Time Activity ◽

Pet Tracers ◽

Arterial Blood ◽

Positron Emission

The development of methods for production of a radiotracer for use in human studies with positron emission tomography (PET) is often a time-consuming process of optimizing radiolabelling yields and handling procedures. Sometimes the radiotracer is not the original drug, but rather a derivative with unknown in vivo pharmacological properties. We have developed a fast and simple method of testing putative new PET tracers in vivo in small animals. The procedure has been validated in rats with different PET tracers with known kinetic and pharmacological properties ([2-18F]2-fluoro-2-deoxy-d-glucose, [ N-methyl-11C]Ro 15-1788, and [15O]butanol). The tracer concentration in arterial blood was continuously measured to obtain the brain input function. Following image reconstruction of the scans, time–activity curves of selected regions of interest were generated. Estimations of CMRglc (1.0 ± 0.2 μmol g−1 min−1), CBF (1.4 ± 0.4 ml g−1 min−1) and transport rate constants for [ N-methyl-11C]Ro 15-1788 (K1 = 0.44 ± 0.01 ml g−1 min−1 and k2 = 0.099 ± 0.005 min−1) as well as calculated first pass extraction (0.32 ±0.1) are in reasonable agreement with literature values. Small animal studies require minimal amounts of radioactivity and can be performed without sterility and toxicology tests. They may serve as a preliminary basis for radiation safety calculations because whole body scans can be performed even with a head scanner. The major advantage of this procedure in comparison to ex vivo autoradiography is that very few experiments are necessary to reliably determine the properties of the blood–brain barrier transport of the radiotracer and the possible whole brain receptor binding characteristics.

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Regional measurement of canine skeletal muscle blood flow by positron emission tomography with H2 15O

Journal of Applied Physiology ◽

10.1152/japplphysiol.00445.2001 ◽

2002 ◽

Vol 92 (4) ◽

pp. 1709-1716 ◽

Cited By ~ 14

Author(s):

Alan J. Fischman ◽

Hongbing Hsu ◽

Edward A. Carter ◽

Yong M. Yu ◽

Ronald G. Tompkins ◽

...

Keyword(s):

Skeletal Muscle ◽

Positron Emission Tomography ◽

Blood Flow ◽

Muscle Blood Flow ◽

Emission Tomography ◽

Time Activity ◽

Skeletal Muscle Blood Flow ◽

Arterial Blood ◽

Positron Emission

Positron emission tomography (PET) with H2 15O was used as an in vivo, relatively noninvasive, quantitative method for measuring regional blood flow to hindlimb skeletal muscle of anesthetized dogs. A hydrooccluder positioned on the femoral artery was used to reduce flow, and high-flow states were produced by local infusion of adenosine. Three to four measurements were made in each animal. Approximately 40 mCi of H2 15O were injected intravenously, and serial images and arterial blood samples were acquired over 2.5 min. Data analysis was performed by fitting tissue and arterial blood time-activity curves to a modified, single-compartment Kety model. The model equation was also solved on a pixel-by-pixel basis to yield maps of regional skeletal muscle blood flow. After each PET determination, flow was measured with radioactive microspheres. Results of the PET measurements demonstrated that basal flow to hindlimb skeletal muscle was 3.83 ± 0.36 ml · min−1 · 100 g−1(mean ± SE). This value was in excellent agreement with the microsphere data, 3.73 ± 0.32 ml · min−1 · 100 g−1( P = 0.69, not significant). Adenosine infusion resulted in flows as high as 30 ml · min−1 · 100 g−1, and the PET and microsphere data were highly correlated over the entire range of flows ( r 2 = 0.98, P < 0.0001). We conclude that muscle blood flow can be accurately measured in vivo by PET with H2 15O and that this approach offers promise for application in human studies of muscle metabolism under varying pathophysiological states.

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Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

EJNMMI Physics ◽

10.1186/s40658-019-0263-x ◽

2019 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Carlos Velasco ◽

Adriana Mota-Cobián ◽

Jesús Mateo ◽

Samuel España

Keyword(s):

Positron Emission Tomography ◽

Blood Sample ◽

Pet Imaging ◽

Spectroscopic Analysis ◽

Gamma Spectroscopy ◽

Emission Tomography ◽

Blood Samples ◽

Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

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