scholarly journals Development and Validation of a PET/SPECT Radiopharmaceutical in Oncology

2021 ◽  
Author(s):  
Federica Pisaneschi ◽  
Nerissa T. Viola
Keyword(s):  
Cancer Biology ◽  
Single Photon ◽  
Photon Emission ◽  
White Paper ◽  
Emission Tomography ◽  
In Vivo Studies ◽  
List Type ◽  
Positron Emission

AbstractIn oncology, biomarker research aimed to provide insights on cancer biology via positron emission tomography (PET) and single photon emission tomography (SPECT) imaging has seen an incredible growth in the past two decades. Despite the increased number of publications on PET/SPECT radiopharmaceuticals, the field lacked standardization of in vitro and in vivo parameters necessary for the characterization of any radiotracer. Through the efforts of the World Molecular Imaging Society Education Committee, this white paper lays down validation studies that are essential to chemically and biologically characterize new radiopharmaceuticals derived from small molecules, peptides or proteins. Finally, a brief overview of the steps toward translation is also presented.Herein, we discuss the following: Chemistry and radiochemistry metrics to establish the identity of the imaging agent. In vitro and in vivo studies to examine the radiotracer’s mechanism of action, which includes target specificity, pharmacokinetics and in vivo metabolism.

In vivo neuropharmacology of schizophrenia

1999 ◽  
Vol 174 (S38) ◽  
pp. 23-33 ◽  
Author(s):  
V. Bigliani ◽  
L. S. Pilowsky
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Emission Tomography ◽  
Binding Assays ◽  
Single Photon Emission ◽  
Positron Emission ◽  
The Brain ◽  
Major Target

Since the introduction of chlorpromazine in the 1950s, followed by the discovery (with in vitro receptor binding assays), in the mid-1970s, that antipsychotic drugs block a subtype of dopamine receptor (D2/D2-like) (Creese et al, 1976) and that affinity for these receptors appears to correlate directly with clinical potency for antipsychotics (Peroutka & Synder, 1980), the study of neurotransmitters and receptors has been a major target of schizophrenia research (Owens, 1996). In 1983, the first visualisation, by positron emission tomography (PET), of the binding of D2 dopamine receptors in the brain of a living human subject was reported (Wagner et al, 1983). Following this, the number of research studies using PET and single photon emission tomography (SPET) has increased enormously.

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

1992 ◽  
Vol 12 (1) ◽  
pp. 147-154 ◽  
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.

scholarly journals Evaluation of 2′-Deoxy-2′-Flouro-5-Methyl-1-β-d-Arabinofuranosyluracil as a Potential Gene Imaging Agent for HSV-tk Expression In Vivo

2002 ◽  
Vol 1 (2) ◽  
pp. 153535002002021
Author(s):  
Mian M. Alauddin ◽  
Atranik Shahinian ◽  
Erlinda M. Gordon ◽  
Peter S. Conti
Keyword(s):  
Emission Tomography ◽  
In Vivo Studies ◽  
In Vitro Experiments ◽  
Tumor Uptake ◽  
Wild Type ◽  
Positron Emission ◽  
Additional Tumor ◽  
Ht 29

2′-Deoxy-2′-flouro-5-methyl-1-β-d-arabinofuranosyluracil (FMAU) has been evaluated in HT-29 cells as a potential positron emission tomography (PET) radiotracer for imaging HSV-tk gene expression in vivo. In vitro experiments demonstrate that the accumulation of [14C]-FMAU in HSV-tk-expressing cells is 2.4-fold ( p < .02), 4.0-fold ( p < .001), and 5.3-fold ( p < .001) higher than the wild-type cells at 1, 3, and 5 hr, respectively. In vivo studies revealed that the tumor uptake in HSV-tk-expressing cells was 2.3-fold ( p < .001), 3.0-fold ( p < .001), and 5.5-fold ( p < .001) higher than the control cells at 1, 2, and 5 hr, respectively. FMAU was found to be more sensitive compared to our earlier studies using 9-[(3-18F-fluoro-1-hydroxy-2-propoxy)methyl]-guanine ([18F]-FHPG) and 9-(4-[18F]-fluoro-3-hydroxy-methylbutyl)guanine ([18F]-FHBG) in the same cell lines, although, the specificity was less than FHBG. These results suggest that while FMAU labeled with PET isotopes may be useful for imaging HSV-tk-expressing tumors in vivo, multitracer studies across additional tumor models are necessary in order to identify an optimal PET radiotracer.

High non-specific binding of the β1-selective radioligand 2-125I-ICI-H

2003 ◽  
Vol 42 (04) ◽  
pp. 173-180 ◽  
Author(s):  
M. P. Law ◽  
K. Kopka ◽  
St. Wagner ◽  
S. Luthra ◽  
V. W. Pike ◽  
...  
Keyword(s):  
Specific Activity ◽  
Single Photon ◽  
Specific Binding ◽  
Photon Emission ◽  
Radiochemical Yield ◽  
Emission Computed Tomography ◽  
Biodistribution Studies ◽  
Positron Emission

Summary: Aim: As results of cardiac biopsies suggest, myocardial β1-adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac β2-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess β-adrenoceptors non-invasively. Among the novel racemic analogues of the established β1-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to β1-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective β1-adrenergic radioligand in cardiac imaging. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac β-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-125I-ICI-H from the silylated precursor 2-SiMe3-ICI-H was established. The specific activity was 80 GBq/µmol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high β1-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac β-adrenoceptors. The radiolabelled counterpart 2-125I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac β1-adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-125I-ICI-H is no suitable radiotracer for imaging in vivo.

Imaging drug action in schizophrenia: research update

2003 ◽  
Vol 18 (S2) ◽  
pp. 32s-37s ◽  
Author(s):  
Marc Laruelle ◽  
Anissa Abi-Dargham
Keyword(s):  
Functional Neuroimaging ◽  
Single Photon ◽  
Photon Emission ◽  
Drug Action ◽  
Emission Tomography ◽  
Single Photon Emission ◽  
Computerised Tomography ◽  
Positron Emission ◽  
And Function

Functional neuroimaging using techniques such as positron emission tomography (PET) and single photon emission computerised tomography (SPECT) provide a direct in vivo assessment of the expression and function of neuroreceptors, transporters and enzymes. This article examines the technical aspects of molecular imaging and the application of those techniques in drug development.

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