On the quantification of [F-18]MPPF binding to 5-HT1A receptors in the human brain

Previous studies have shown that 4-(2 ' -methoxyphenyl)-1 [2 '-(N-2 "- pyridinyl)-p- [F-18]fluorobenzamido]ethylpiperazine ([F-18]MPPF) binds with high selectivity to serotonin (5-HT1A) receptors in man. However, in these studies, the calculation of the binding potential (BP, which equals receptor density divided by equilibrium dissociation constant) used a metabolite-corrected arterial input. The aim of this study was to determine whether metabolite correction and arterial sampling are essential for the assessment of BP. Methods: Five analytic methods using full datasets obtained from 6 healthy volunteers were compared. In addition, the clinical applicability of these methods was appraised. Three methods were based on Logan analysis of the dynamic PET data using metabolite-corrected and uncorrected arterial plasma input and cerebellar input. The other 2 methods consisted of a simplified reference tissue model and standard compartmental modeling. Results: A high correlation was found between BP calculated with Logan analysis using the metabolite-corrected plasma input (used as the reference method for this study) and Logan analysis using either the uncorrected arterial plasma input (r(2) = 0.95, slope = 0.85) or cerebellar input (r(2) = 0.98, slope = 0.91), A high correlation was also found between our reference method and the simplified reference tissue model (r(2) = 0.94, slope = 0.92). In contrast, a poor correlation was observed between our reference method and the standard compartmental model (r(2) = 0.45, slope = 1.59). Conclusion: These results indicate that neither metabolite analysis nor arterial sampling is necessary for clinical evaluation of BP in the human brain with [18F]MPPF. Both the Logan analysis method with cerebellar input and the simplified reference tissue method can be applied clinically

On the quantification of [F-18]MPPF binding to 5-HT1A receptors in the human brain

Previous studies have shown that 4-(2 ' -methoxyphenyl)-1 [2 '-(N-2 "- pyridinyl)-p- [F-18]fluorobenzamido]ethylpiperazine ([F-18]MPPF) binds with high selectivity to serotonin (5-HT1A) receptors in man. However, in these studies, the calculation of the binding potential (BP, which equals receptor density divided by equilibrium dissociation constant) used a metabolite-corrected arterial input. The aim of this study was to determine whether metabolite correction and arterial sampling are essential for the assessment of BP. Methods: Five analytic methods using full datasets obtained from 6 healthy volunteers were compared. In addition, the clinical applicability of these methods was appraised. Three methods were based on Logan analysis of the dynamic PET data using metabolite-corrected and uncorrected arterial plasma input and cerebellar input. The other 2 methods consisted of a simplified reference tissue model and standard compartmental modeling. Results: A high correlation was found between BP calculated with Logan analysis using the metabolite-corrected plasma input (used as the reference method for this study) and Logan analysis using either the uncorrected arterial plasma input (r(2) = 0.95, slope = 0.85) or cerebellar input (r(2) = 0.98, slope = 0.91), A high correlation was also found between our reference method and the simplified reference tissue model (r(2) = 0.94, slope = 0.92). In contrast, a poor correlation was observed between our reference method and the standard compartmental model (r(2) = 0.45, slope = 1.59). Conclusion: These results indicate that neither metabolite analysis nor arterial sampling is necessary for clinical evaluation of BP in the human brain with [18F]MPPF. Both the Logan analysis method with cerebellar input and the simplified reference tissue method can be applied clinically

Imaging beta-adrenoceptors in the human brain with (S)-1'-[F-18]fluorocarazolol

We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[F-18]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pK(i) beta(1) 9.4, beta(2) 10.0, 5HT(1A) 7.4, 5HT(1B) 8.1) and rapidly crosses the blood-brain barrier. Methods: The (S)-[F-18]fluorocarazolol (74 MBq, >37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk, The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode. Results: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum, Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain, The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals. Conclusion: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease

Long axial field of view PET scanners: a road map to implementation and new possibilities

In this contribution, several opportunities and challenges for long axial field of view (LAFOV) PET are described. It is an anthology in which the main issues have been highlighted. A consolidated overview of the camera system implementation, business and financial plan, opportunities and challenges is provided. What the nuclear medicine and molecular imaging community can expect from these new PET/CT scanners is the delivery of more comprehensive information to the clinicians for advancing diagnosis, therapy evaluation and clinical research

Imaging beta-adrenoceptors in the human brain with (S)-1'-[F-18]fluorocarazolol

We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral beta-adrenoceptors because (S)-1'-[F-18]fluorocarazolol has a higher affinity to beta-adrenoceptors than to serotonergic receptors (pK(i) beta(1) 9.4, beta(2) 10.0, 5HT(1A) 7.4, 5HT(1B) 8.1) and rapidly crosses the blood-brain barrier. Methods: The (S)-[F-18]fluorocarazolol (74 MBq, >37 TBq/mmol) was intravenously administered to healthy volunteers on two separate occasions with an interval of at least 1 wk, The initial injection was without pretreatment, but before the second injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg orally, during 18 hr). The brain was studied with a PET camera in dynamic mode. Results: Uptake of radioactivity delineated gray matter and was particularly high in the posterior cingulate, precuneus and striatum, Low uptake occurred in the thalamus, whereas the lowest uptake was observed in the white matter of the corpus callosum. After pindolol pretreatment, uptake was reduced and its distribution became homogeneous throughout the brain, The ratio of total-to-nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer intervals. Conclusion: Fluorocarazolol is the first radioligand that can visualize cerebral beta-adrenoceptors and may enable monitoring of these binding sites during disease