Search

The chemokine receptor 4 (CXCR4) has been an attractive molecular target for tumor imaging, because it is overexpressed in many tumor types and involved in tumor progression and metastasis. The purpose of this study is to examine the CXCR4 targeting properties of 99mTc‐labeled AMD3465, a small molecule antagonist of CXCR4. 99mTc‐AMD3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 hours. In vitro cell binding experiments were performed with Chinese hamster ovary (CHO), MCF‐7 (breast cancer), and CHO‐CXCR4 (CHO stably transfected to express CXCR4) cell lines. Small animal single photon emission computed tomography/computed tomography imaging studies in nude mice bearing MCF‐7 and CHO xenografts showed that the uptakes of the radiotracer in MCF‐7 tumors were significantly higher than those in the CXCR4‐negative CHO tumors (P < 0.05), and the MCF‐7 tumors uptake could be blocked with an excess of unlabeled AMD3465 (P < 0.05). These results suggested that 99mTc‐AMD3465 could be a potential single photon emission computed tomography radiotracer for CXCR4 imaging. [ABSTRACT FROM AUTHOR]

Folate receptor is an ideal target for tumor-specific diagnostic and therapeutic. The aim of this study was to synthesize 99mTc-labeled folate-polyamidoamine dendrimer modified with 2-hydrazinonicotinic acid (99mTc- HP3 FA) for FR imaging. The 99mTc- HP3 FA conjugate was prepared using N-tris-(hydroxymethyl)-methylglycine and trisodium triphenylphosphine-3,3′,3″-trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro-single-photon emission computed tomography/ CT imaging were performed. The radiolabeled 99mTc- HP3 FA conjugate was prepared with high radiolabeling yield, good stability, and water solubility (log P = −1.70 ± 0.21). In cell uptake study, the radiolabeled conjugate showed high uptakes in the FR-abundant KB cells and could be blocked significantly by excess folic acid. The 7721 cells which served as control group substantially had no uptakes. The results of micro-single-photon emission computed tomography/ CT imaging exhibited that high accumulation of activity was found in FR-overexpressed KB tumor, and the tumor-to-muscle ratio was approximately 25.78, while, using free FA as inhibitor, the uptakes of 99mTc- HP3 FA in KB tumor and kidney were obviously inhibited. In summary, a new radiocompound was synthesized successfully with specific FR targeting ability. The feasibility of 99mTc- HP3 FA for early diagnosis of FR-positive tumors with non-invasive single-photon emission computed tomography imaging was demonstrated and the possibility of imaging-guided drug delivery based on multifunctional polyamidoamine will be studied in the future. [ABSTRACT FROM AUTHOR]

To develop a novel progesterone receptor-targeting probe for positron emission tomography imaging, an ethisterone derivative [18F]EAEF was designed and prepared in high decay-corrected radiochemical yield (30-35%) with good radiochemical purity (>98%). [18F]EAEF is a lipophilic tracer (log P = 0.53 ± 0.06) with very good stability in saline and serum. In the biodistribution study, high radioactivity accumulation of [18F]EAEF were found in uterus (5.73 ± 1.83% ID/g) and ovary (4.05 ± 0.73% ID/g) at 2 hr postinjection (p.i.), which have high progesterone receptor expression after treated with estradiol, while the muscle background has very low uptake (0.50 ± 0.17% ID/g). For positron emission tomography imaging, [18F]EAEF showed high uptake in progesterone receptor-positive MCF-7 tumor (3.15 ± 0.07% ID/g at 2 hr p.i.) with good tumor to muscle ratio (2.90), and obvious lower tumor uptakes were observed in MCF-7 with EAEF blocking (1.84 ± 0.05% ID/g at 2 hr p.i.) or in progesterone receptor-negative MDA-MB-231 tumor (1.80 ± 0.03% ID/g at 2 hr p.i.). Based on the good stability and specificity of [18F]EAEF, it may be a good candidate for imaging progesterone receptor and worth further investigation. [ABSTRACT FROM AUTHOR]

The chemokine receptor 4 (CXCR4) has been an attractive molecular target for tumor imaging, because it is overexpressed in many tumor types and involved in tumor progression and metastasis. The purpose of this study is to examine the CXCR4 targeting properties of 99m Tc-labeled AMD3465, a small molecule antagonist of CXCR4. 99m Tc-AMD3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 hours. In vitro cell binding experiments were performed with Chinese hamster ovary (CHO), MCF-7 (breast cancer), and CHO-CXCR4 (CHO stably transfected to express CXCR4) cell lines. Small animal single photon emission computed tomography/computed tomography imaging studies in nude mice bearing MCF-7 and CHO xenografts showed that the uptakes of the radiotracer in MCF-7 tumors were significantly higher than those in the CXCR4-negative CHO tumors (P < 0.05), and the MCF-7 tumors uptake could be blocked with an excess of unlabeled AMD3465 (P < 0.05). These results suggested that 99m Tc-AMD3465 could be a potential single photon emission computed tomography radiotracer for CXCR4 imaging., (Copyright © 2018 John Wiley & Sons, Ltd.)

Extracellular matrix (ECM) accumulation in liver fibrosis is caused by the activation of hepatic stellate cells (HSCs). The goal of this study was to develop a 99m Tc-labeled N-acetylglucosamine (GlcNAc) that specifically interacts with desmin and vimentin expressed on activated HSCs to monitor the progression and prognosis of liver fibrosis using single-photon emission computed tomography (SPECT) imaging. Methods: GlcNAc-conjugated polyethylenimine (PEI) was first prepared and radiolabeled with 99m Tc. Noninvasive SPECT imaging with 99m Tc-GlcNAc-PEI was used to assess liver fibrosis in a carbon tetrachloride (CCl 4 ) mouse model. The liver uptake value (LUV) of 99m Tc-GlcNAc-PEI was measured by drawing the region of interest (ROI) of the whole liver as previously suggested. The LUV of the CCl 4 groups was compared with that of the olive oil group. Next, we estimated the correlation between the results of SPECT imaging and physiological indexes. After treatment with clodronate liposome, the LUV of 99m Tc-GlcNAc-PEI in fibrotic mice was compared with that in control mice. Results: 99m Tc-GlcNAc-PEI is a hydrophilic compound with high radiochemical purity (>98%) and good stability. It could specifically target desmin and vimentin on the surface of activated HSCs with high affinity (the K d values were 53.75 ± 9.50 nM and 20.98 ± 3.56 nM, respectively). The LUV of 99m Tc-GlcNAc-PEI was significantly different between the CCl 4 and control groups as early as 4 weeks of CCl 4 administration (3.30 ± 0.160 vs 2.34 ± 0.114%/cc; P ˂ 0.05). There was a strong correlation between the LUV and Sirius Red quantification (R = 0.92, P ˂ 0.001). Compared with control, clodronate liposome treatment reduced the LUV of 99m Tc-GlcNAc-PEI (4.62 ± 0.352 vs 2.133 ± 0.414%/cc; P ˂ 0.05). Conclusion: 99m Tc-GlcNAc-PEI SPECT/CT was useful in assessing liver fibrosis and monitoring the treatment response., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

This study aims to develop a new folate receptor (FR)-targeting agent for SPECT imaging with improved contrast and evaluate the modification strategies of multimerization and/or PEGylation in the development of new radio-folates. A series of novel folate derivatives have been synthesized and radiolabeled with 99m Tc using tricine and TPPTS as coligands. To better investigate their pharmacokinetics, cell uptake, biodistribution, and microSPECT/CT imaging were evaluated. Four radioligands displayed high KB cell uptake after incubation for 2 and 4 h. Presaturated with excess folic acid (FA) resulted in a significant blocking effect in KB cells, indicating specificity of these radioligands toward FR. Biodistribution and microSPECT imaging studies in KB tumor-bearing mice showed that the folate conjugate 99m Tc-HYNFA with poly(ethylene glycol) (PEG) and triazole linkage displayed the highest tumor uptake (16.30 ± 2.01 %ID/g at 2 h p.i. and 14.9 ± 0.62 %ID/g at 4 h p.i. in mice biodistribution) and best imaging contrast, indicating promising application prospect. More interestingly, the in vivo performance of this monomeric 99m Tc-HYNFA was much better than that of FA multimers and non-PEGylated monomers, suggesting that multimerization may not be a feasible method for the design of radio-folates. PEG linkage rather than FA multimerization should be taken into consideration in the development of folate-based radiopharmaceuticals in the future.

Folate receptor is an ideal target for tumor-specific diagnostic and therapeutic. The aim of this study was to synthesize 99m Tc-labeled folate-polyamidoamine dendrimer modified with 2-hydrazinonicotinic acid ( 99m Tc-HP 3 FA) for FR imaging. The 99m Tc-HP 3 FA conjugate was prepared using N-tris-(hydroxymethyl)-methylglycine and trisodium triphenylphosphine-3,3',3″-trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro-single-photon emission computed tomography/CT imaging were performed. The radiolabeled 99m Tc-HP 3 FA conjugate was prepared with high radiolabeling yield, good stability, and water solubility (logP = -1.70 ± 0.21). In cell uptake study, the radiolabeled conjugate showed high uptakes in the FR-abundant KB cells and could be blocked significantly by excess folic acid. The 7721 cells which served as control group substantially had no uptakes. The results of micro-single-photon emission computed tomography/CT imaging exhibited that high accumulation of activity was found in FR-overexpressed KB tumor, and the tumor-to-muscle ratio was approximately 25.78, while, using free FA as inhibitor, the uptakes of 99m Tc-HP 3 FA in KB tumor and kidney were obviously inhibited. In summary, a new radiocompound was synthesized successfully with specific FR targeting ability. The feasibility of 99m Tc-HP 3 FA for early diagnosis of FR-positive tumors with non-invasive single-photon emission computed tomography imaging was demonstrated and the possibility of imaging-guided drug delivery based on multifunctional polyamidoamine will be studied in the future., (© 2016 John Wiley & Sons A/S.)

To develop a novel progesterone receptor-targeting probe for positron emission tomography imaging, an ethisterone derivative [ 18 F]EAEF was designed and prepared in high decay-corrected radiochemical yield (30-35%) with good radiochemical purity (>98%). [ 18 F]EAEF is a lipophilic tracer (logP = 0.53 ± 0.06) with very good stability in saline and serum. In the biodistribution study, high radioactivity accumulation of [ 18 F]EAEF were found in uterus (5.73 ± 1.83% ID/g) and ovary (4.05 ± 0.73% ID/g) at 2 hr postinjection (p.i.), which have high progesterone receptor expression after treated with estradiol, while the muscle background has very low uptake (0.50 ± 0.17% ID/g). For positron emission tomography imaging, [ 18 F]EAEF showed high uptake in progesterone receptor-positive MCF-7 tumor (3.15 ± 0.07% ID/g at 2 hr p.i.) with good tumor to muscle ratio (2.90), and obvious lower tumor uptakes were observed in MCF-7 with EAEF blocking (1.84 ± 0.05% ID/g at 2 hr p.i.) or in progesterone receptor-negative MDA-MB-231 tumor (1.80 ± 0.03% ID/g at 2 hr p.i.). Based on the good stability and specificity of [ 18 F]EAEF, it may be a good candidate for imaging progesterone receptor and worth further investigation., (© 2016 John Wiley & Sons A/S.)

Fluorinated polyethylenimine derivative labeled with radionuclide (99m) Tc is developed as a (19) F MRI/SPECT/PA multifunctional imaging agent with good asialoglycoprotein receptors (ASGPR)-targeting ability. This multifunctional agent is safe and suitable for (19) F MRI/SPECT/PA imaging and has the potential to detect hepatic diseases and to assess liver function, which provide powerful support for the development of personalized and precision medicine., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)