In Vivo Labeling of Serum Albumin for PET.
The purpose of this study was to develop a novel in vivo albumin-labeling method to allow PET of cardiac function after myocardial infarction and vascular leakage and increased permeability in inflammatory diseases and malignant tumors.


METHODS
To label albumin in vivo, we synthesized a NOTA (1,4,7-triazacyclononane-N,N',N″-triacetic acid)-conjugated truncated form of Evans blue (NEB). (18)F labeling was achieved by the formation of an (18)F-aluminum fluoride ((18)F-AlF) complex, and (64)Cu labeling was obtained by a standard chelation method. Sixty-minute dynamic PET imaging was performed on normal mice to evaluate the distribution of (18)F-AlF-NEB, which was compared with in vitro-labeled mouse serum albumin ((18)F-fluorobenzyl-MSA). Electrocardiography-gated PET imaging was performed in a mouse model of myocardial infarction. Both dynamic and static PET scans were obtained in a mouse inflammation model induced by local injection of turpentine to evaluate vascular leakage. Tumor permeability was studied by dynamic and late-point static PET using (64)Cu-NEB in a UM-22B xenograft model.


RESULTS
NEB was successfully synthesized, and (18)F labeling including work-up took about 20-30 min, with a radiochemical purity greater than 95% without the need for high-performance liquid chromatography purification. Most of the radioactivity was retained in the circulation system at 60 min after injection (26.35 ± 1.52 percentage injected dose per gram [%ID/g]). With electrocardiography-gated PET, ventricles of the heart and major arteries were clearly visualized. The myocardial infarction mice showed much lower left ventricular ejection fraction than the control mice. Inflammatory muscles showed significantly higher tracer accumulation than the contralateral healthy ones. UM-22B tumor uptake of (64)Cu-NEB gradually increased with time (5.73 ± 1.11 %ID/g at 1 h and 8.03 ± 0.77 %ID/g at 2 h after injection).


CONCLUSIONS
The distribution and local accumulation of serum albumin can be noninvasively visualized and quantified by (18)F-AlF-NEB and (64)Cu-NEB PET. The simple labeling and broad applications make these imaging probes attractive for clinical translation.
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
Gang
G
Niu
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
Lixin
L
Lang
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
Dale O
DO
Kiesewetter
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland shawn.chen@nih.gov.
Ying
Y
Ma
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
Zhongchan
Z
Sun
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
Ning
N
Guo
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
Jinxia
J
Guo
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
Chenxi
C
Wu
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland shawn.chen@nih.gov.
Xiaoyuan
X
Chen
D000818:Animals; D002199:Capillary Permeability; D004562:Electrocardiography; D006321:Heart / Q000000981:diagnostic imaging / Q000502:physiology; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D011854:Radiochemistry; D012709:Serum Albumin
D012709:Serum Albumin
Evans blue; PET; in vivo labeling; serum albumin; vascular permeability