178181-33-4Relevant articles and documents
A novel radiofluorinated agouti-related protein for tumor angiogenesis imaging
Jiang, Han,Moore, Sarah J.,Liu, Shuanglong,Liu, Hongguang,Miao, Zheng,Cochran, Frank V.,Liu, Yang,Tian, Mei,Cochran, Jennifer R.,Zhang, Hong,Cheng, Zhen
, p. 673 - 681 (2013)
A novel protein scaffold based on the cystine knot domain of the agouti-related protein (AgRP) has been used to engineer mutants that can bind to the αvβ3 integrin receptor with high affinity and specificity. In the current study, an 18F-labeled AgRP mutant (7C) was prepared and evaluated as a positron emission tomography (PET) probe for imaging tumor angiogenesis. AgRP-7C was synthesized by solid phase peptide synthesis and site-specifically conjugated with 4-nitrophenyl 2- 18/19F-fluoropropionate (18/19F-NFP) to produce the fluorinated peptide, 18/19F-FP-AgRP-7C. Competition binding assays were used to measure the relative affinities of AgRP-7C and 19F-FP- AgRP-7C to human glioblastoma U87MG cells that overexpress α vβ3 integrin. In addition, biodistribution, metabolic stability, and small animal PET imaging studies were conducted with 18F-FP-AgRP-7C using U87MG tumor-bearing mice. Both AgRP-7C and 19F-FP-AgRP-7C specifically competed with 125I-echistatin for binding to U87MG cells with half maximal inhibitory concentration (IC 50) values of 9.40 and 8.37 nM, respectively. Non-invasive small animal PET imaging revealed that 18F-FP-AgRP-7C exhibited rapid and good tumor uptake (3.24 percentage injected dose per gram [% ID/g] at 0.5 h post injection [p.i.]). The probe was rapidly cleared from the blood and from most organs, resulting in excellent tumor-to-normal tissue contrasts. Tumor uptake and rapid clearance were further confirmed with biodistribution studies. Furthermore, co-injection of 18F-FP-AgRP-7C with a large molar excess of blocking peptide c(RGDyK) significantly inhibited tumor uptake in U87MG xenograft models, demonstrating the integrin-targeting specificity of the probe. Metabolite assays showed that the probe had high stability, making it suitable for in vivo applications. 18F-FP-AgRP-7C exhibits promising in vivo properties such as rapid tumor targeting, good tumor uptake, and excellent tumor-to-normal tissue ratios, and warrants further investigation as a novel PET probe for imaging tumor angiogenesis.
A novel aliphatic 18F-labeled probe for PET imaging of melanoma
Liu, Hongguang,Liu, Shuanglong,Miao, Zheng,Jiang, Han,Deng, Zixin,Hong, Xuechuan,Cheng, Zhen
, p. 3384 - 3391 (2013)
Radiofluorinated benzamide and nicotinamide analogues are promising molecular probes for the positron emission tomography (PET) imaging of melanoma. Compounds containing aromatic (benzene or pyridine) and N,N- diethylethylenediamine groups have been successfully used for development of melanin targeted PET and single-photon emission computed tomography (SPECT) imaging agents for melanoma. The objective of this study was to determine the feasibility of using aliphatic compounds as a molecular platform for the development of a new generation of PET probes for melanoma detection. An aliphatic N,N-diethylethylenediamine precursor was directly coupled to a radiofluorination synthon, p-nitrophenyl 2-18F-fluoropropionate (18F-NFP), to produce the probe N-(2-(diethylamino)ethyl)-2- 18F-fluoropropanamide (18F-FPDA). The melanoma-targeting ability of 18F-FPDA was further evaluated both in vitro and in vivo through cell uptake assays, biodistribution studies, and small animal PET imaging in C57BL/6 mice bearing B16F10 murine melanoma tumors. Beginning with the precursor 18F-NFP, the total preparation time for 18F-FPDA, including the final high-performance liquid chromatography purification step, was approximately 30 min, with a decay-corrected radiochemical yield of 79.8%. The melanin-targeting specificity of 18F-FPDA was demonstrated by significantly different uptake rates in tyrosine-treated and untreated B16F10 cells in vitro. The tumor uptake of 18F-FPDA in vivo reached 2.65 ± 0.48 %ID/g at 2 h postinjection (p.i.) in pigment-enriched B16F10 xenografts, whereas the tumor uptake of 18F-FPDA was close to the background levels, with rates of only 0.37 ± 0.07 %ID/g at 2 h p.i. in the nonpigmented U87MG tumor mouse model. Furthermore, small animal PET imaging studies revealed that 18F-FPDA specifically targeted the melanotic B16F10 tumor, yielding a tumor-to-muscle ratio of approximately 4:1 at 1 h p.i. and 7:1 at 2 h p.i. In summary, we report the development of a novel 18F-labeled aliphatic compound for melanoma imaging that can be easily synthesized in high yields using the radiosynthon 18F-NFP. The PET probe 18F-FPDA exhibits high B16F10 tumor-targeting efficacy and favorable in vivo pharmacokinetics. Our study demonstrates that aliphatic compounds can be used as a new generation molecular platform for the development of novel melanoma targeting agents. Further evaluation and optimization of 18F-FPDA for melanin targeted molecular imaging are therefore warranted.
Imino acid PET imaging agent and its preparation method and application
-
Paragraph 0024; 0025, (2017/01/12)
The invention discloses an amino acid positron emission tomography (PET) imaging agent, and a preparation method and application thereof. The imaging agent belongs to the field of N-substituted positron nuclide labeled glutamic acid compound and has a str
