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 99mTc-HMPAO under physiologic conditions and monitored in vivo distribution of 99mTc-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with 99mTc-HMPAO for 1 hr incubation, followed by removal of free 99mTc-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with 99mTc-HMPAO, the radiochemical purity of 99mTc-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in 99mTc-HMPAO-ENVs. 99mTc-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 99mTc-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with 99mTc-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.
Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the emergence of 'self-invented' terms. In order to address these concerns, an international Working Group on 'Nomenclature in Radiopharmaceutical Chemistry and related areas' was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field. Upon open consultation, the following consensus guidelines were agreed, which aim to.
The fact that some brain tumors show hypo- or isometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has caused problems in the detection of primary or recurrent tumors and in the differentiation from benign lesions. We investigated the usefulness of carbon-11 methionine PET in characterizing brain lesions under these conditions. 11C-methionine PET was performed in 45 patients with brain lesions (in 34 for initial diagnosis and in 11 for detection of recurrence) that showed hypo- or isometabolism compared with normal brain tissue on FDG PET. Ten minutes after the injection of 555-740 MBq of 11C-methionine, attenuation-corrected brain images were obtained with a dedicated PET scanner. The brain lesions comprised 24 gliomas, five metastatic brain tumors, four meningiomas, two other brain tumors and ten benign lesions (including three cases of cysticercosis, two cases of radiation necrosis, one tuberculous granuloma, one hemangioma, one benign cyst, and one organizing infarction). Proliferative activity was measured using the Ki-67 immunostaining method in glioma tissues. Thirty-one of 35 brain tumors (89% sensitivity) showed increased 11C-methionine uptake despite iso- or hypometabolism on FDG PET. By contrast, all ten benign lesions showed decreased or normal 11C-methionine uptake (100% specificity). Twenty-two of 24 gliomas (92%) showed increased 11C-methionine uptake, the extent and degree of which exceeded 18F-FDG uptake, and the 11C-methionine uptake correlated with the proliferation index (r=0.67). The mean (+/-SD) uptake ratios of glioma to normal brain on FDG and 11C-methionine PET were 0.92+/-0.34 and 2.54+/-1.25, respectively. All metastatic tumors except one showed intense 11C-methionine uptake in the entire tumor or in the peripheral margin of the tumor. In meningiomas, 11C-methionine uptake showed a variable increase. In conclusion, brain lesions that show hypo- or isometabolism on FDG PET can be detected and differentiated with high sensitivity and good contrast using 11C-methionine PET. 11C-methionine PET can provide additional information when used in combination with FDG PET in the evaluation of these patients.
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