Novel PET Imaging of Atherosclerosis with 68 Ga-Labeled NOTA-Neomannosylated Human Serum Albumin

Kang

et al. 2017

Theranostics

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The diagnosis of myocarditis traditionally relies on invasive endomyocardial biopsy but none of the imaging studies so far are specific for infiltration of the inflammatory cells itself. We synthesized 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA) by conjugating human serum albumin with mannose, followed by conjugation with NOTA and labeling it with 68Ga. The efficacy of 68Ga-NOTA-MSA positron emission tomography (PET) for imaging myocardial inflammation was tested in a rat myocarditis model. A significant number of mannose receptor-positive inflammatory cells infiltrated the myocardium in both human and rat myocarditis tissue. 68Ga-NOTA-MSA uptake was upregulated in organs of macrophage accumulation, such as liver, spleen, bone marrow and myocardium (0.32 (0.31~0.33) for normal versus 1.02 (0.86~1.06) for myocarditis (median (range), SUV); n=4~6 per group, p-value=0.01). 68Ga-NOTA-MSA uptake in the left ventricle was upregulated in myocarditis compared with normal rats (2.29 (1.42~3.40) for normal versus 4.18 (3.43~6.15) for myocarditis (median (range), average standard uptake value ratio against paraspinal muscle); n=6 per group, p-value<0.01), which was downregulated in rats with cyclosporine-A treated myocarditis (3.69 (2.59~3.86) for myocarditis versus 2.28 (1.76~2.60) for cyclosporine-A treated myocarditis; n=6 per group, p-value<0.01). The specificity of the tracer was verified by administration of excess non-labeled MSA. 68Ga-NOTA-MSA uptake was significantly enhanced earlier in the evolution of myocarditis before any signs of inflammation could be seen on echocardiography. These results demonstrate the potential utility of visualizing infiltration of mannose receptor-positive macrophages with 68Ga-NOTA-MSA PET in the early diagnosis of as well as in the monitoring of treatment response of myocarditis.

Section: Discussionmentioning

confidence: 77%

Noninvasive Imaging of Myocardial Inflammation in Myocarditis using ⁶⁸Ga-tagged Mannosylated Human Serum Albumin Positron Emission Tomography

Kang

et al. 2017

Theranostics

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“…Several radioligands, including those targeting inducible nitric oxide synthase (21), folate receptor-b (22,23), CD206 (24,25), and LOX-1 (26)(27)(28), have been developed to visualize macrophages, and several of these have also been used to image acute inflammation. Though present ubiquitously, TSPO expression is elevated in immunologically activated leukocytes such as microglia and macrophages (29) and has been used as a molecular target for imaging of neuroinflammation (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Biodistribution and Radiation Dosimetry of ¹²⁴I-DPA-713, a PET Radiotracer for Macrophage-Associated Inflammation

et al. 2018

Whole-body PET/CT was performed using I-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. Healthy subjects aged 18-65 y underwent whole-body PET/CT either at 4, 24, and 48 h or at 24, 48, and 72 h after intravenous injection of I-DPA-713. Time-activity curves were generated and used to calculate organ time-integrated activity coefficients for each subject. The resulting time-integrated activity coefficients provided input data for calculation of organ absorbed doses and effective dose for each subject using OLINDA. Subjects were genotyped for the polymorphism rs6971, and plasma protein binding of I-DPA-713 was measured. Three male and 3 female adults with a mean age of 40 ± 19 y were imaged. The mean administered activity and mass were 70.5 ± 5.1 MBq (range, 62.4-78.1 MBq) and 469 ± 34 ng (range, 416-520 ng), respectively. There were no adverse or clinically detectable pharmacologic effects in any of the 6 subjects. No changes in vital signs, laboratory values, or electrocardiograms were observed. I-DPA-713 cleared rapidly (4 h after injection) from the lungs, with hepatic elimination and localization to the gastrointestinal tract. The mean effective dose over the 6 subjects was 0.459 ± 0.127 mSv/MBq, with the liver being the dose-limiting organ (0.924 ± 0.501 mGy/MBq). The percentage of free radiotracer in blood was approximately 30% at 30 and 60 min after injection. I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults.

“…99m Tc-MSA, developed for SLN imaging 10 , was shown to bind to the mannose receptor on the macrophage surface 20 – 22 . Thus, 99m Tc-MSA may serve as an excellent agent for SLN imaging.…”

Section: Discussionmentioning

confidence: 99%

Naphthol Blue Black and 99mTc-Labeled Mannosylated Human Serum Albumin (99mTc-MSA) Conjugate as a Multimodal Lymph Node Mapping Nanocarrier

Kim

et al. 2018

Sci Rep

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99mTc-labeled mannosylated human serum albumin (MSA) has been reported as a sentinel lymph node (SLN)-imaging agent by binding to macrophages in the LNs. By conjugating it with blue dye, we developed a new multimodal radio-nanocarrier by visual investigation, fluorescence imaging, and single photon emission computed tomography (SPECT)/computed tomography (CT). Binding affinities of seven blue dyes to MSA were tested. According to the spectroscopic study and visual inspection of MSA-bound dyes, naphthol blue black (NBB) was selected as the best candidate of multimodal agent. Thus, 99mTc-MSA-NBB conjugate was prepared and further investigated using mice. After footpad injection, it showed high popliteal LN accumulation at 1 h. SPECT/CT also showed high popliteal as well as inguinal LN uptakes at 10 min that sustained until 2 h. In conclusion, we prepared a multimodal SLN imaging radio-nanocarrier, 99mTc-MSA-NBB conjugate, and confirmed its excellency as a multimodal probe for SLN mapping.