An Error Analysis of Pulmonary Vascular Permeability Measurements Made with Positron Emission Tomography

1990 ◽  
pp. 147-154
Author(s):  
D. P. Schuster ◽  
J. Markham ◽  
J. Kaplan ◽  
T. Warfel ◽  
M. Mintun
Keyword(s):  
Positron Emission Tomography ◽  
Error Analysis ◽  
Vascular Permeability ◽  
Emission Tomography ◽  
Pulmonary Vascular Permeability ◽  
Positron Emission

scholarly journals [68Ga]ABY-028: an albumin-binding domain (ABD) protein-based imaging tracer for positron emission tomography (PET) studies of altered vascular permeability and predictions of albumin-drug conjugate transport

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Emma Jussing ◽  
Li Lu ◽  
Jonas Grafström ◽  
Tetyana Tegnebratt ◽  
Fabian Arnberg ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Vascular Permeability ◽  
Ex Vivo ◽  
Circulatory System ◽  
Binding Domain ◽  
The Body ◽  
Emission Tomography ◽  
Albumin Binding ◽  
Positron Emission

Abstract Background Albumin is commonly used as a carrier platform for drugs to extend their circulatory half-lives and influence their uptake into tissues that have altered permeability to the plasma protein. The albumin-binding domain (ABD) protein, which binds in vivo to serum albumin with high affinity, has proven to be a versatile scaffold for engineering biopharmaceuticals with a range of binding capabilities. In this study, the ABD protein equipped with a mal-DOTA chelator (denoted ABY-028) was radiolabeled with gallium-68 (68Ga). This novel radiotracer was then used together with positron emission tomography (PET) imaging to examine variations in the uptake of the ABD-albumin conjugate with variations in endothelial permeability. Results ABY-028, produced by peptide synthesis in excellent purity and stored at − 20 °C, was stable for 24 months (end of study). [68Ga]ABY-028 could be obtained with labeling yields of > 80% and approximately 95% radiochemical purity. [68Ga]ABY-028 distributed in vivo with the plasma pool, with highest radioactivity in the heart ventricles and major vessels of the body, a gradual transport over time from the circulatory system into tissues and elimination via the kidneys. Early [68Ga]ABY-028 uptake differed in xenografts with different vascular properties: mean standard uptake values (SUVmean) were initially 5 times larger in FaDu than in A431 xenografts, but the difference decreased to 3 after 1 h. Cutaneously administered, vasoactive nitroglycerin increased radioactivity in the A431 xenografts. Heterogeneity in the levels and rates of increases of radioactivity uptake was observed in sub-regions of individual MMTV-PyMT mammary tumors and in FaDu xenografts. Higher uptake early after tracer administration could be observed in lower metabolic regions. Fluctuations in the increased permeability for the tracer across the blood-brain-barrier (BBB) direct after experimentally induced stroke were monitored by PET and the increased uptake was confirmed by ex vivo phosphorimaging. Conclusions [68Ga]ABY-028 is a promising new tracer for visualization of changes in albumin uptake due to disease- and pharmacologically altered vascular permeability and their potential effects on the passive uptake of targeting therapeutics based on the ABD protein technology.

scholarly journals Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography

Theranostics ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. 2363-2376 ◽  
Author(s):  
Haojun Chen ◽  
Xiao Tong ◽  
Lixin Lang ◽  
Orit Jacobson ◽  
Bryant C. Yung ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Vascular Permeability ◽  
Blood Volume ◽  
Emission Tomography ◽  
Positron Emission

scholarly journals Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[18F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects

1993 ◽  
Vol 13 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Hiroto Kuwabara ◽  
Paul Cumming ◽  
Jakob Reith ◽  
Gabriel Léger ◽  
Mirko Diksic ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Error Analysis ◽  
Frontal Cortex ◽  
Transport Coefficients ◽  
Fixed Ratio ◽  
Emission Tomography ◽  
Dopa Decarboxylase ◽  
Decarboxylase Activity ◽  
Positron Emission

DOPA decarboxylase is the enzyme directly responsible for the synthesis of the neurotransmitters dopamine and serotonin, and indirectly of noradrenaline, in brain. We used the decarboxylation coefficient ( kD3) of 6-[18F]fluoro-DOPA (FDOPA) to denote the relative activity of l-DOPA decarboxylase in vivo in the human brain. To determine the relative enzyme activity with positron emission tomography (PET), we evaluated the model that separates the metabolism into compartments of nondiffusible and diffusible (i.e., transient) tracer metabolites. Error analysis indicated that the least-squares optimization alone was not sufficient to yield accurate estimates of kD3 in the presence of the inherent error of PET. To improve the accuracy of the kD3 estimates by optimizing the number of parameters, we introduced biological constraints which included a tracer partition volume ( Ve) common to frontal cortex and striatum, and a fixed ratio ( q) between the blood–brain barrier transport coefficients of O-methyl-[18F]fluoro-DOPA and FDOPA, the two sources of radioactivity in plasma. We found that a two-step analysis yielded sufficiently accurate estimates of kD3. The two steps include the initial estimation of the partition volume in frontal cortex and the subsequent use of this value to determine kD3 in striatum and other structures. We studied twelve healthy controls (age 45 ± 15 years). The average kD3 value was 0.081 ± 0.024 min−1 (coefficient of variation (COV) 30%) for caudate nucleus, 0.074 ± 0.013 min“1 (COV 18%) for putamen, and 0.010 ± 0.005 min−1 (COV 50%) for cerebral cortex.

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