Effects of Temperature on the in Vitro Binding of 3H‐Raclopride to Rat Striatal Dopamine‐D2 Receptors

Hall, Håkan; Wedel, Ilse; Sällemark, Maria

doi:10.1111/j.1600-0773.1988.tb00922.x

Cited by 25 publications

(7 citation statements)

References 15 publications

(2 reference statements)

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“…However, previous pharmacological assays were performed almost exclusively at 41C or RT, whereas our assays were performed at 371C (to generate data that are potentially more readily related to in vivo PET data). It is not unusual or unexpected for temperature to affect the binding properties of radioligands (Hall et al, 1988(Hall et al, , 1990). Our autoradiography studies, which were performed at RT, produced K d values very similar to those reported previously (Doble et al, 1987;Miyazawa et al, 1998;Rao and Butterworth, 1997;Venneti et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Two Binding Sites for [³H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation

Owen

Howell

Tang

et al. 2010

J Cereb Blood Flow Metab

190

194

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[11C]PBR28, a radioligand targeting the translocator protein (TSPO), does not produce a specific binding signal in approximately 14% of healthy volunteers. This phenomenon has not been reported for [11C]PK11195, another TSPO radioligand. We measured the specific binding signals with [3H]PK11195 and [3H]PBR28 in brain tissue from 22 donors. Overall, 23% of the samples did not generate a visually detectable specific autoradiographic signal with [3H]PBR28, although all samples showed [3H]PK11195 binding. There was a marked reduction in the affinity of [3H]PBR28 for TSPO in samples with no visible [3H]PBR28 autoradiographic signal ( K i=188±15.6 nmol/L), relative to those showing normal signal ( K i=3.4±0.5 nmol/L, P<0.001). Of this latter group, [3H]PBR28 bound with a two-site fit in 40% of cases, with affinities ( K i) of 4.0±2.4 nmol/L (high-affinity site) and 313±77 nmol/L (low-affinity site). There was no difference in Kd or Bmax for [3H]PK11195 in samples showing no [3H]PBR28 autoradiographic signal relative to those showing normal [3H]PBR28 autoradiographic signal. [3H]PK11195 bound with a single site for all samples. The existence of three different binding patterns with PBR28 (high-affinity binding (46%), low-affinity binding (23%), and two-site binding (31%)) suggests that a reduction in [11C]PBR28 binding may not be interpreted simply as a reduction in TSPO density. The functional significance of differences in binding characteristics warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Two Binding Sites for [³H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation

Owen

Howell

Tang

et al. 2010

J Cereb Blood Flow Metab

190

194

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“…The reported in vitro value for fallypride is K D ‫ס‬ 0.03nM (t ‫ס‬ 25°C) (Mukherjee et al, 1995). For in vitro measurement of K D , substituted benzamides are known to have a large temperature dependence (Hall et al, 1988). This limits the accuracy of in vitro with in vivo K D correlations.…”

Section: In Vivo Parameters Of [F-18]fallypridementioning

confidence: 99%

Measuring the in Vivo Binding Parameters of [¹⁸F]-Fallypride in Monkeys Using a PET Multiple-Injection Protocol

Christian

Narayanan

Shi

et al. 2004

J Cereb Blood Flow Metab

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The goal of this work was to quantify the in vivo transport and binding parameters of [F-18]fallypride and the D2/D3 receptor density (B'max) in both the striatal (putamen, caudate, ventral striatum) and extrastriatal regions (thalamus, amygdala, cerebellum, temporal and frontal cortices) of the rhesus monkey brain. Multiple-injection PET experimental protocols with injections of radiolabeled and unlabeled doses of fallypride were used to estimate the K1, k2, kon/VR, koff and B'max kinetic parameters. The experimental design was chosen using the D-optimal criterion to maximize the precision of the estimated binding parameters for the various brain regions. There was a significant range in B'max for the putamen (27 pmol/mL), caudate (23 pmol/mL), ventral striatum (14 pmol/mL), thalamus (1.8 pmol/mL) and amygdala (0.9 pmol/mL). Significant receptor binding was also found in the cortical regions. Knowledge of these in vivo rate constants serves as a necessary step in using [F-18]fallypride PET to measure D2/D3 receptor density and drug occupancy in clinical research applications. We believe the precise parameter estimates derived from these complicated experimental protocols are necessary for proper application of drug occupancy and clinical research studies with [F-18]fallypride, which often rely on the validity of assumptions regarding the model parameters.

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“…The receptor binding studies were performed according to a previously described procedure. 27 The corpus striatum was homogenized in 50 mM Tris-HCl buffer (pH 7.7 at 25 °C) and centrifuged at 48000g for 10 min. The pellet was resuspended and centrifuged as before.…”

Section: -[3-[4-(o-butoxyphenyl)piperazin-1-yl]propyl]-13-dioxoperhyd...mentioning

confidence: 99%

Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 5. Study of the Physicochemical Influence of the Pharmacophore on 5-HT_1A/α₁-Adrenergic Receptor Affinity: Synthesis of a New Derivative with Mixed 5-HT_1A/D₂ Antagonist Properties

et al. 2000

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In this paper we have designed and synthesized a test series of 32 amide arylpiperazine derivatives VI in order to gain insight into the physicochemical influence of the pharmacophores of 5-HT(1A) and alpha(1)-adrenergic receptors. The training set was designed applying a fractional factorial design using six physicochemical descriptors. The amide moiety is a bicyclohydantoin or a diketopiperazine (X = -(CH(2))(3)-, -(CH(2))(4)-; m = 0, 1), the spacer length is 3 or 4 methylene units, which are the optimum values for both receptors, and the aromatic substituent R occupies the ortho- or meta-position and has been selected from a database of 387 substituents using the EDISFAR program. The 5-HT(1A) and alpha(1)-adrenergic receptor binding affinities of synthesized compounds VI (1-32) have been determined. This data set has been used to derive classical quantitative structure-activity relationships (QSAR) and neural networks models for both receptors (following paper). A comparison of these models gives information for the design of the new ligand EF-7412 (46) (5-HT(1A): K(i) = 27 nM; alpha(1): K(i) > 1000 nM). This derivative displays affinity for the dopamine D(2) receptor (K(i) = 22 nM) and is selective versus all other receptors examined (5-HT(2A), 5-HT(3), 5-HT(4) and Bz; K(i) > 1000 nM). EF-7412 (46) acts as an antagonist in vivo in pre- and postsynaptic 5-HT(1A) receptor sites and as an antagonist in the dopamine D(2) receptor. Thus, EF-7412 (46) is a derivative with mixed 5-HT(1A)/D(2) antagonist properties and this derivative could be useful as a pharmacological tool.

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Effects of Temperature on the in Vitro Binding of ³H‐Raclopride to Rat Striatal Dopamine‐D₂ Receptors

Cited by 25 publications

References 15 publications

Two Binding Sites for [³H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation

Two Binding Sites for [³H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation

Measuring the in Vivo Binding Parameters of [¹⁸F]-Fallypride in Monkeys Using a PET Multiple-Injection Protocol

Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 5. Study of the Physicochemical Influence of the Pharmacophore on 5-HT_1A/α₁-Adrenergic Receptor Affinity: Synthesis of a New Derivative with Mixed 5-HT_1A/D₂ Antagonist Properties

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Effects of Temperature on the in Vitro Binding of 3H‐Raclopride to Rat Striatal Dopamine‐D2 Receptors

Cited by 25 publications

References 15 publications

Two Binding Sites for [3H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation

Two Binding Sites for [3H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation

Measuring the in Vivo Binding Parameters of [18F]-Fallypride in Monkeys Using a PET Multiple-Injection Protocol

Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 5. Study of the Physicochemical Influence of the Pharmacophore on 5-HT1A/α1-Adrenergic Receptor Affinity: Synthesis of a New Derivative with Mixed 5-HT1A/D2 Antagonist Properties

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Effects of Temperature on the in Vitro Binding of ³H‐Raclopride to Rat Striatal Dopamine‐D₂ Receptors

Two Binding Sites for [³H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation

Two Binding Sites for [³H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation

Measuring the in Vivo Binding Parameters of [¹⁸F]-Fallypride in Monkeys Using a PET Multiple-Injection Protocol

Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 5. Study of the Physicochemical Influence of the Pharmacophore on 5-HT_1A/α₁-Adrenergic Receptor Affinity: Synthesis of a New Derivative with Mixed 5-HT_1A/D₂ Antagonist Properties