Simulating the effect of venous dispersion on distribution volume measurements from the Logan plot

Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [11C]PBR28. In order to study the effects of age, sex, and obesity on TSPO binding and to determine whether this binding can be accurately assessed using fewer radio high-performance liquid chromatography (radio-HPLC) measurements of arterial blood samples, we created a database of 48 healthy subjects who had undergone [11C]PBR28 scans (23 high-affinity binders (HABs) and 25 mixed-affinity binders (MABs), 20 F/28 M, age: 40.6 ± 16.8 years). After analysis by Logan plot using 23 metabolite-corrected arterial samples, total distribution volume ( VT) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake ( VND) as 1.40 mL · cm−3, which generated a specific-to-nondisplaceable ratio ( BPND) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. VT increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, VT did not correlate with body mass index and was not affected by sex. These results underscore which patient characteristics should be accounted for during [11C]PBR28 studies and suggest ways to perform such studies more easily and with fewer blood samples.

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Equilibrium versus Compartmental Analysis for Assessment of the Vesicular Monoamine Transporter Using (+)-α-[11C]Dihydrotetrabenazine (DTBZ) and Positron Emission Tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199709000-00001 ◽

1997 ◽

Vol 17 (9) ◽

pp. 919-931 ◽

Cited By ~ 58

Author(s):

Robert A. Koeppe ◽

Kirk A. Frey ◽

Akito Kume ◽

Roger Albin ◽

Michael R. Kilbourn ◽

...

Keyword(s):

Positron Emission Tomography ◽

Steady State ◽

Close Agreement ◽

Compartmental Analysis ◽

Distribution Volume ◽

Emission Tomography ◽

Vesicular Monoamine Transporter ◽

Monoamine Transporter ◽

Logan Plot ◽

Positron Emission

This work compares equilibrium to kinetic analysis of positron emission tomography data for the assessment of vesicular monoamine transporter (VMAT2) binding density using (+)-α-[11C]dihydrotetrabenazine ((+)-α-[11C]DTBZ). Studies were performed for 80 minutes after intravenous administration of 18 ± 1 mCi (+)-α-[11C]DTBZ on 9 young control subjects, 20 to 45 years of age. A 9-mCi bolus was injected over the first minute of the study, whereas the remaining 9 mCi were infused at a constant rate over the following 79 minutes. Steady-state was reached in both blood and brain by approximately 30 minutes after initiation of the study. Nonlinear least-squares analysis using two- and three-compartment models, weighted integral analysis using a two-compartment configuration, and Logan plot analysis all yielded kinetic estimates of the total tissue distribution volume, DVtot(kin). These results were compared with equilibrium distribution volume estimates, DVtot(eq), calculated from the tissue to metabolite corrected arterial plasma concentration ratio after 30 minutes. Kinetic modeling results from this study were in close agreement with prior bolus-injection (+)-α-[11C]DTBZ studies. In the current study, coefficients of variation in DVtot(kin) (19% to 23% across regions) and DVtot(eq) (18% to 22%) were nearly identical. Equilibrium estimates of DVtot were slightly lower than kinetic estimates, averaging 5% ± 9% lower ( P = 0.04, paired t test) in regions of high binding density (caudate and putamen), but only 2% ± 6% ( P = 0.09) in lower binding density regions (cortex, thalamus, cerebellum). DVtot(eq) estimates, however, still correlated highly with DVtot(kin) estimates ( r = 0.977−0.989). Steady-state conditions can be achieved in both tissue and blood by 30 minutes, and the tissue-to-blood ratios of (+)-α-[11C]DTBZ at equilibrium yield DVtot(eq) measures that are in close agreement with DVtot(kin) estimates. Thus, a simple, easily tolerated protocol using a loading bolus followed by continuous infusion can provide excellent measures of VMAT2 binding.

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Noninvasive Measurement of [11C]PiB Distribution Volume Using Integrated PET/MRI

Diagnostics ◽

10.3390/diagnostics10120993 ◽

2020 ◽

Vol 10 (12) ◽

pp. 993

Author(s):

Hidehiko Okazawa ◽

Masamichi Ikawa ◽

Tetsuya Tsujikawa ◽

Akira Makino ◽

Tetsuya Mori ◽

...

Keyword(s):

Standardized Uptake Value ◽

Input Function ◽

Distribution Volume ◽

Mri Segmentation ◽

Reference Tissue ◽

Pittsburgh Compound B ◽

Quantitative Measurements ◽

Logan Plot ◽

Static Data ◽

Early Alzheimer’S Disease

A noninvasive image-derived input function (IDIF) method using PET/MRI was applied to quantitative measurements of [11C] Pittsburgh compound-B (PiB) distribution volume (DV) and compared with other metrics. Fifty-three patients suspected of early dementia (71 ± 11 y) underwent 70 min [11C]PiB PET/MRI. Nineteen of them (68 ± 11 y) without head motion during the scan were enrolled in this study and compared with 16 age-matched healthy controls (CTL: 68 ± 11 y). The dynamic frames reconstructed from listmode PET data were used for DV calculation. IDIF with metabolite correction was applied to the Logan plot method, and DV was normalized into DV ratio (DVR) images using the cerebellar reference (DVRL). DVR and standardized uptake value ratio (SUVR) images were also calculated using the reference tissue graphical method (DVRr) and the 50–70 min static data with cerebellar reference, respectively. Cortical values were compared using the 3D-T1WI MRI segmentation. All patients were assigned to the early Alzheimer’s disease (eAD) group because of positive [11C]PiB accumulation. The correlations of regional values were better for DVRL vs. DVRr (r2 = 0.97) than for SUVR vs. DVRr (r2 = 0.88). However, all metrics clearly differentiated eAD from CTL with appropriate thresholds. Noninvasive quantitative [11C]PiB PET/MRI measurement provided equivalent DVRs with the two methods. SUVR images showed acceptable results despite inferior variability and image quality to DVR images.

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Dual Cannulation of Free-Swimming Atlantic Salmon, Salmo salar

Canadian Journal of Fisheries and Aquatic Sciences ◽

10.1139/f84-062 ◽

1984 ◽

Vol 41 (3) ◽

pp. 519-521 ◽

Cited By ~ 3

Author(s):

D. J. Nichols ◽

M. Weisbart

Keyword(s):

Atlantic Salmon ◽

Salmo Salar ◽

Distribution Volume ◽

Blood Sampling ◽

Free Swimming ◽

Atlantic Salmon Salmo Salar ◽

Volume Measurements

We describe a technique for enduring (>1 mo) dual cannulation of large, free-swimming Atlantic salmon, Salmo salar. Repeated blood sampling is possible without disturbance of the fish and the technique is suitable for studies that involve administration of radiolabeled substances for kinetic and distribution volume measurements.

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Evaluation of the total distribution volume of 18F-FBPA in normal tissues of healthy volunteers by non-compartmental kinetic modeling

Annals of Nuclear Medicine ◽

10.1007/s12149-019-01427-9 ◽

2019 ◽

Vol 34 (3) ◽

pp. 155-162

Author(s):

Victor Romanov ◽

Kayako Isohashi ◽

Galal Alobthani ◽

Rouaa Beshr ◽

Genki Horitsugi ◽

...

Keyword(s):

Healthy Volunteers ◽

Goodness Of Fit ◽

Boron Concentration ◽

Distribution Volume ◽

Post Injection ◽

Residual Distribution ◽

Activity Data ◽

Normal Tissues ◽

Logan Plot ◽

The Right

Abstract Objective Boron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[18F]-fluoro-L-phenylalanine (18F-FBPA) PET has been employed to estimate 10B accumulation in target tumors and normal tissues if 10B borono-L-phenylalanine (10B-BPA) is used as a boron carrier. The purpose of the current study was to evaluate the total distribution volume (Vt) of 18F-FBPA in normal organs of healthy volunteers by kinetic analysis and to estimate boron concentration in normal organs for the therapeutic dose of 10B-BPA using obtained Vt values. Methods Six healthy volunteers were injected with 18F-FBPA (3–5 MBq/kg), and 7 PET-CT scans were performed subsequently. 18F-FBPA radioactivity in whole blood and plasma was measured before, and eight times after the injection. PET images were analyzed by PMOD software. Twelve volumetric regions of interest including the brain, heart, right lung, spleen, liver, parotid salivary glands, esophagus, stomach, pancreas, intestines, and bone marrow were drawn manually for each subject and analyzed with the Logan plot and two Ichise multilinear analyses (MA1 and MA2). The better model was defined by several goodness-of-fit parameters and residual distribution. After Vt values had been derived, boron concentration was estimated in ppm for the 10B-BPA-fructose (10B-BPA-fr) dose 30 g 1 and 2 h post-injection using Vt and interpolated plasma activity data. Results The Ichise MA2 model showed the best fit among all models. Akaike Information Criterion (AIC) was the lowest for the Ichise’s MA2 in all regions (mean AIC value − 14.0) comparing to the other models (Logan plot mean AIC 31.4; Ichise MA1 model mean AIC − 4.2). Mean Vt values of the Ichise MA2 model ranged from 0.94 ± 0.14 ml/ml in the pancreas to 0.16 ± 0.02 ml/ml in the right lung. Estimated boron concentration for 10B-BPA-fr had the highest value in the pancreas (14.0 ± 1.9 ppm 1 h after, and 5.7 ± 1.7 ppm 2 h after the 18F-FBPA administration) and the lowest value in the right lung (2.4 ± 0.3 ppm 1 h, and 1.0 ± 0.3 ppm 2 h post-injection). Conclusion The 10B concentration in normal tissues was best estimated using Vt values of 18F-FBPA with the Ichise multilinear analysis 2 (MA2). Trail registry The UMIN clinical trial number: UMIN000022850.

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Effect of acute hyaluronidase treatment of the glycocalyx on tracer-based whole body vascular volume estimates in mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00842.2012 ◽

2013 ◽

Vol 114 (9) ◽

pp. 1132-1140 ◽

Cited By ~ 11

Author(s):

Jurgen W. G. E. VanTeeffelen ◽

Judith Brands ◽

Ben J. A. Janssen ◽

Hans Vink

Keyword(s):

Barrier Properties ◽

Distribution Volume ◽

The Body ◽

Endothelial Glycocalyx ◽

Whole Body ◽

Differential Distribution ◽

Vascular Volume ◽

Body Distribution ◽

Volume Measurements ◽

Tracer Dilution

The endothelial glycocalyx forms a hyaluronan-containing interface between the flowing blood and the endothelium throughout the body. By comparing the systemic distribution of a small glycocalyx-accessible tracer vs. a large circulating plasma tracer, the size-selective barrier properties of the glycocalyx have recently been utilized to estimate whole body glycocalyx volumes in humans and animals, but a comprehensive validation of this approach has been lacking at the moment. In the present study, we compared, in anesthetized, ventilated C57Bl/6 mice, the whole body distribution of small (40 kDa) dextrans (Texas Red labeled; Dex40) vs. that of intermediate (70 kDa) and large (500 kDa) dextrans (both FITC labeled; Dex70 and Dex500, respectively) using tracer dilution and vs. that of circulating plasma, as derived from the dilution of fluorescein-labeled red blood cells and large-vessel hematocrit. The contribution of the glycocalyx was evaluated by intravenous infusion of a bolus of the enzyme hyaluronidase. In saline-treated control mice, distribution volume (in ml) differed between tracers ( P < 0.05; ANOVA) in the following order: Dex40 (0.97 ± 0.04) > Dex70 (0.90 ± 0.04) > Dex500 (0.81 ± 0.10) > plasma (0.71 ± 0.02), resulting in an inaccessible vascular volume, i.e., compared with the distribution volume of Dex40, of 0.03 ± 0.01, 0.15 ± 0.04, and 0.31 ± 0.05 ml for Dex70, Dex500, and plasma, respectively. In hyaluronidase-treated mice, Dex70 and Dex40 volumes were not different from each other, and inaccessible vascular volumes for Dex500 (0.03 ± 0.03) and plasma (0.14 ± 0.05) were smaller ( P < 0.05) than those in control animals. Clearance of Dex70 and Dex500 from the circulation was enhanced ( P < 0.05) in hyaluronidase-treated vs. control mice. These results indicate that the glycocalyx contributes to size-dependent differences in whole body vascular distribution of plasma solutes in mice. Whole body vascular volume measurements based on the differential distribution of glycocalyx-selective tracers appear appropriate for the detection of generalized glycocalyx degradation in experimental animals and humans.

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