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ImmunoPET imaging, which combining the specificity of monoclonal antibody and high sensitivity of PET imaging, blazes new trails of molecular imaging modality. In recent years, clinical translation and application of immunoPET imaging strategies have been flourishing, as a result, facilitating early and non-invasive diagnosis of numerous human tumors, patient stratification before monoclonal antibody therapy and radiation dose estimation prior to radioimmunotherapy. Here, we summarize the most recent clinical evidence of immunoPET in tumor diagnosis and therapy.
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Objective:To prepare 89Zr labeled Daratumumab and evaluate its feasibility in the imaging diagnosis of multiple myeloma (MM). Methods:According to the principle of 89Y (p, n) 89Zr nuclear reaction, 89Zr was produced by cyclotron solid target system (30 μA, 1.5 h) and automatic purification module. The radionuclide purity, half-life and impurity metal ion concentration were detected. Desferrioxamine (DFO) was coupled with Daratumumab and then chelated with 89Zr to prepare 89Zr-DFO-Daratumumab. The quality control analyses of three consecutive batches were carried out. Pharmacokinetic evaluation and 89Zr-DFO-Daratumumab microPET/CT imaging were performed in normal rabbits and orthotopic myeloma mouse models, respectively. The SUV in situ myeloma and that in normal bone were compared by independent-sample t test. Results:About 560 MBq of 89Zr was obtained, and there were only two characteristic energy peaks of 89Zr (909 keV and 511 keV) by γ spectrometer. The half-life of 89Zr was 78.2 h, and the content of metal impurities was small. 89Zr-DFO-Daratumumab was prepared with pH of 7.2, radiochemical purity of more than 99%, good stability in vitro, and sterility and endotoxin tests were passed. Pharmacokinetic studies in rabbits showed that 89Zr-DFO-Daratumumab was gradually distributed from blood to liver, spleen, kidney and bone joints over time and metabolism. The results of microPET/CT imaging in orthotopic myeloma mouse models showed that the SUVs of 89Zr-DFO-daratumumab in situ myeloma were significantly higher than those in normal bone (2 h: 0.22±0.02 vs 0.06±0.00; 1 d: 0.38±0.01 vs 0.08±0.00; t values: 8.89, 21.90, both P=0.001). Conclusion:89Zr and 89Zr-DFO-daratumumab are successfully prepared, and relevant quality control and biological evaluation in vivo and in vitro are completed, which verify the feasibility of 89Zr-DFO-Daratumumab in the imaging diagnosis of MM, thus laying a foundation for clinical transformation.
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Objective To investigate the effects of microRNA (miR)106a on the proliferation, apoptosis, migration and invasion of thyroid cancer cells in vitro.Methods 8505C and CGTH-W3 cell lines were used in the study.Overexpression and inhibition of miR106a were achieved by transfection of lentiviral vectors.The changes of gene expression were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis.Cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively.The caspase-9 activities in parental CGTH-W3 and 8505C cells and transfected sublines were measured.Wound healing and Transwell invasion assays were performed to determine cell migration and invasion.Two-sample t test and one-way analysis of variance were used to analyze the data.Results The level of miR106a in 8505C was up-regulated when compared to that in CGTH-W3 cells (t=10.28, P<0.01).Scrambled control and miR106a(-) were also successfully transfected into cells.Inhibition of miR106a suppressed cell viability, migration and invasion while promoted apoptosis and caspase-9 activity of 8505C cells, with significant differences among 8505C, 8505C-control, 8505C-miR106a(-) cells (F=147.0, 19.2, 100.3, 537.8, 804.3;all P<0.01).Overexpression of miR106a promoted cell viability, migration and invasion while inhibited apoptosis and caspase-9 activity of CGTH-W3 cells, with significant differences among CGTH-W3, CGTH-W3-control, CGTH-W3-miR106a(+) cells(F=9.2, 13.3, 622.8, 12.3, 19.6, all P<0.01).In addition, miR106a may up-regulate the expression of MEKK2 and p-ERK1/2.Conclusion Acting as an onco-miR, miR106a might promote the proliferation, migration and invasion of thyroid cancer cells and inhibit their apoptosis in vitro.
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DTC is the most common endocrine carcinoma and its routine treatment consists of total thyroidectomy and 131I thyroid remnant ablation.Currently,standard follow-up for DTC comprises Tg measurement and neck ultrasound as well as an additional radioiodine scan when indicated.As thyroid cells are assumed to be the only source of Tg in serum,circulating Tg serves as an excellent marker of persistent or recurrent disease in DTC follow-up.With the development of highly sensitive Tg assays,now it is possible to detect very low Tg concentrations which reflect minimal amounts of thyroid tissue without the need for TSH stimulation.This review is to introduce clinical implications of highly sensitive Tg assays.