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Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using (99m)Tc-HMPAO.

ABSTRACT: Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with (99m)Tc-HMPAO under physiologic conditions and monitored in vivo distribution of (99m)Tc-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with (99m)Tc-HMPAO for 1?hr incubation, followed by removal of free (99m)Tc-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with (99m)Tc-HMPAO, the radiochemical purity of (99m)Tc-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in (99m)Tc-HMPAO-ENVs. (99m)Tc-HMPAO-ENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5?hr. SPECT/CT images of the mice injected with (99m)Tc-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with (99m)Tc-HMPAO showed high brain uptake until 5?hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.

SUBMITTER: Hwang DW

PROVIDER: S-EPMC4620485 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using (99m)Tc-HMPAO.

Hwang Do Won DW Choi Hongyoon H Jang Su Chul SC Yoo Min Young MY Park Ji Yong JY Choi Na Eun NE Oh Hyun Jeong HJ Ha Seunggyun S Lee Yun-Sang YS Jeong Jae Min JM Gho Yong Song YS Lee Dong Soo DS

Scientific reports 20151026

Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with (99m)Tc-HMPAO under physiologic conditions and monitored in vivo distribution of (99m)Tc-HMPAO-ENVs using SPECT/C ...[more]

PMID: 26497063

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Project description:BackgroundMolecular breast imaging (MBI) performed with 99mTc sestamibi has been shown to be a valuable technique for the detection of breast cancer. Alternative radiotracers such as 99mTc maraciclatide may offer improved uptake in breast lesions. The purpose of this study was to compare relative performance of 99mTc sestamibi and 99mTc maraciclatide in patients with suspected breast cancer, using a high-resolution dedicated gamma camera for MBI. Women with breast lesions suspicious for malignancy were recruited to undergo two MBI examinations-one with 99mTc sestamibi and one with 99mTc maraciclatide. A radiologist interpreted MBI studies in a randomized, blinded fashion to assign an assessment score (1-5) and measured lesion size. Lesion-to-background (L/B) ratio was measured with region-of-interest analysis.ResultsAmong 39 analyzable patients, 21 malignant tumors were identified in 21 patients. Eighteen of 21 tumors (86%) were seen on 99mTc sestamibi MBI and 19 of 21 (90%) were seen on 99mTc maraciclatide MBI (p = 1). Tumor extent measured with both radiopharmaceuticals correlated strongly with pathologic size (99mTc sestamibi, r = 0.84; 99mTc maraciclatide, r = 0.81). The L/B ratio in detected breast cancers was similar for the two radiopharmaceuticals: 1.55 ± 0.36 (mean ± S.D.) for 99mTc sestamibi and 1.62 ± 0.37 (mean ± S.D.) for 99mTc maraciclatide (p = 0.53). No correlation was found between the L/B ratio and molecular subtype for 99mTc sestamibi (r s = 0.12, p = 0.63) or 99mTc maraciclatide (r s = -0.12, p = 0.64). Of 20 benign lesions, 10 (50%) were seen on 99mTc sestamibi and 9 of 20 (45%) were seen on 99mTc maraciclatide images (p = 0.1). The average L/B ratio for benign lesions was 1.34 ±0.40 (mean ±S.D.) for 99mTc sestamibi and 1.41 ±0.52 (mean ±S.D.) for 99mTc maraciclatide (p = 0.75). Overall diagnostic performance was similar for both radiopharmaceuticals. AUC from ROC analysis was 0.83 for 99mTc sestamibi and 0.87 for 99mTc maraciclatide (p = 0.64).Conclusions99mTc maraciclatide offered comparable lesion uptake to 99mTc sestamibi, in both malignant and benign lesions. There was good correlation between lesion extent and uptake measured from both radiopharmaceuticals. 99mTc maraciclatide offered a marginal (but not significant) improvement in sensitivity over 99mTc sestamibi. Our findings did not support an association between the uptake of either radiopharmaceutical and tumor molecular subtype.Trial registrationClinicalTrials.gov, NCT00888589.

Project description:ObjectiveSingle-photon emission computed tomography (SPECT) with the tracer 99m Tc-HMPAO is a method to visualize the cerebral hyperperfusion during an epileptic seizure and thus localize the epileptogenic zone and seizure propagation. Subtraction of interictal from Ictal SPECT Co-registered to MRI (SISCOM) visualizes areas with relative increases in cerebral blood flow. The purpose of this retrospective study is to explore the added value of visualizing areas of hypoperfusion as well as hyperperfusion, so-called reversed SISCOM.MethodsFifty-six patients operated for epilepsy who had been investigated with SISCOM were included in the analysis. The patients were divided into two groups based on seizure duration after tracer injection, above or below 30 s. The preoperative SISCOM description was compared to the area of resection and given a concordance score. The 56 SISCOM were recalculated visualizing also areas of hypoperfusion and again compared to the site of resection using the same scale of concordance. The reversed SISCOM were categorized into three subgroups: "Altered Conclusion," "Confirmed Conclusion," and "Adds Nothing." If an area of hyperperfusion had an area of hypoperfusion in close proximity, it was re-interpreted as noise, thus possibly altering the conclusion. If the areas of hypoperfusion were in the opposite hemisphere it was interpreted as confirming factor. Further the concordance scores from conventional SISCOM and reversed SISCOM was compared to surgical outcome to explore the difference in sensitivity, positive predictive value (PPV), and odds ratio.ResultsIn approximately half of the cases reversed SISCOM added additional value, meaning either altered the conclusion or confirmed the conclusion. The sensitivity, PPV, and odds ratio was also better in the subgroup of long, >30 s seizure duration after injection, and got worse in the group with short, <30 s seizure duration after injection.SignificanceAdding reversed SISCOM performed better than conventional SISCOM at predicting good surgical outcome.

Dataset Information

Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using (99m)Tc-HMPAO.

Publications

Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using (99m)Tc-HMPAO.

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