scholarly journals A Pretargeted Imaging Strategy for EGFR Positive Colorectal Carcinoma via the Modulation of Tz-radioligand Pharmacokinetics

2020 ◽  
Author(s):  
Lin Qiu ◽  
Hui Tan ◽  
Qingyu Lin ◽  
Zhan Si ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Radiochemical Purity ◽  
Binding Assay ◽  
Tumor Imaging ◽  
Hct116 Cell ◽  
Size Exclusion ◽  
Liquid Chromatograph ◽  
Imaging Results ◽  
Imaging Strategy

Abstract Objective: Previously, we successfully developed a 6-hydrazinonicotinic acid (HYNIC)-modified terazine (Tz) derivative (HYNIC-PEG11-Tz) and labeled with Technetium-99m (99mTc) with a high radiochemical purity. The pretargeted imaging strategy using Atezolizumab-TCO/99mTc-HYNIC-PEG11-Tz is a powerful tool for evaluating Programmed Cell Death Ligand-1 (PD-L1) expression in xenograft mice tumor models. However, the surplus unclicked 99mTc-HYNIC-PEG11-Tz is cleared somewhat sluggishly through the intestines. This is certainly not an ideal situation for imaging for abdominal tumors, especially for colorectal cancer. In order to shift the excretion of the Tz-radioligand to the renal system, we have sought to develop a novel Tz-radioligand by add a polypeptide linker between HYNIC and PEG11. Methods: A polypeptide-modified Tz (HYNIC-Polypeptide-PEG11-Tz) was synthesized and radiolabeled with 99mTc, and the Cetuximab was covalently modified with transcyclooctene (TCO-NHS). The stability of 99mTc-HYNIC-Polypeptide-PEG11-Tz was evaluated in vitro, and its blood pharmacokinetic test was performed in vivo. Determination of the n-octanol/PBS distribution coefficient was performed on 99mTc-HYNIC-PEG11-Tz and 99mTc-HYNIC-Polypeptide-PEG11-Tz to determine the effect of linker modification on their hydrophobicity. In vitro ligation reactivity of 99mTc-HYNIC-Polypeptide-PEG11-Tz towards Cetuximab-TCO was tested. Pretargeted HCT116 cell immunoreactivity binding assay was evaluated. The biodistribution and imaging of 99mTc-HYNIC-Polypeptide-PEG11-Tz was performed to observe the clear pathway of this novel Tz-radioligand. Pretargeted biodistribution of three different accumulation intervals (24 h, 48 h, and 72 h) was performed to determine the optimal pretargeted interval time in nude mice bearing HCT116 tumor xenografts. Comparison of pretargeted (Cetuximab-TCO 48h/99mTc-HYNIC-PEG11-Tz 6h) and (Cetuximab-TCO 48h/ 99mTc-HYNIC-Polypeptide-PEG11-Tz 6h) imaging was performed to show the effect of the two Tz-radioligands with different excretion pathway on tumor imaging. Results: HYNIC-Polypeptide-PEG11-Tz was successfully radiosynthesized with 99mTc, and a radiochemical purity greater than 95% were obtained as confirmed by radio high-performance liquid chromatography (HPLC). 99mTc-HYNIC-Polypeptide-PEG11-Tz showed favorable stability in NS, PBS, and FBS and rapid blood clearance in mice. Liquid chromatograph-mass spectrometer (LC-MS) indicated the presence of an average 8.1 TCO moieties per Cetuximab. Size exclusion HPLC revealed almost complete reaction between Cetuximab-TCO and 99mTc-HYNIC-Polypeptide-PEG11-Tz in vitro, with the 8:1 Tz-to-mAb reaction providing a conversion yield of 87.83±3.27%. Pretargeted cell immunoreactivity binding assay showed high affinity to HCT116 cells. The biodistribution and imaging of 99mTc-HYNIC-Polypeptide-PEG11-Tz demonstrated that the Tz-radioligand was cleared through kidneys. After allowing 24h, 48h and 72h for accumulation of Cetuximab-TCO in HCT116 tumor, pretargeted biodistribution revealed an uptake of the radiotracer in the tumor with tumor-to-blood ratio of 0.83, 1.40, and 1.15, respectively. Both pretargeted (Cetuximab-TCO 48h/99mTc-HYNIC-PEG11-Tz 6h) and (Cetuximab-TCO 48h/ 99mTc-HYNIC-Polypeptide-PEG11-Tz 6h) imaging delineated the HCT116 tumor clearly. However, pretargeted imaging strategy using Cetuximab-TCO 48h/99mTc-HYNIC-Polypeptide-PEG11-Tz 6h) could be used for diagnosing colorectal cancer since the surplus unclicked 99mTc-HYNIC-Polypeptide-PEG11-Tz is cleared through urinary system and produces low abdominal uptake background. Conclusion: We developed a novel pretargeted imaging strategy (Cetuximab-TCO/99mTc-HYNIC-Polypeptide-PEG11-Tz) for imaging colorectal cancer since the surplus unclicked 99mTc-HYNIC-Polypeptide-PEG11-Tz produces low abdominal uptake background, which broadens the application scope of pretargeted imaging strategy.

scholarly journals A Pretargeted Imaging Strategy for EGFR Positive Colorectal Carcinoma via the Modulation of Tz-radioligand Pharmacokinetics

2020 ◽  
Author(s):  
Lin Qiu ◽  
Hui Tan ◽  
Qingyu Lin ◽  
Zhan Si ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Molecular Probes ◽  
Ideal Situation ◽  
Imaging Results ◽  
Imaging Strategy ◽  
Xenograft Mice ◽  
The Stability ◽  
In Vitro Stability

Abstract Objective: Previously, we successfully developed a pretargeted imaging strategy (Atezolizumab-TCO/99mTc-HYNIC-PEG11-Tz), which is a powerful tool for evaluating Programmed Cell Death Ligand-1 (PD-L1) expression in xenograft mice tumor models. However, the surplus unclicked 99mTc-HYNIC-PEG11-Tz is cleared somewhat sluggishly through the intestines. This is certainly not an ideal situation for imaging for colorectal cancer (CRC). In order to shift the excretion of the Tz-radioligand to the renal system, we have sought to develop a novel Tz-radioligand by adding a polypeptide linker between HYNIC and PEG11. Methods: Pretargeted molecular probes 99mTc-HYNIC-Polypeptide-PEG11-Tz and Cetuximab-TCO were synthesized. The stability of 99mTc-HYNIC-Polypeptide-PEG11-Tz was evaluated in vitro, and its blood pharmacokinetic test was performed in vivo. In vitro ligation reactivity of 99mTc-HYNIC-Polypeptide-PEG11-Tz towards Cetuximab-TCO was tested. The biodistribution and imaging of 99mTc-HYNIC-Polypeptide-PEG11-Tz was performed to observe the clear pathway of this novel Tz-radioligand. Pretargeted biodistribution of three different accumulation intervals was performed to determine the optimal pretargeted interval time. Comparison of pretargeted (Cetuximab-TCO 48 h/99mTc-HYNIC-PEG11-Tz 6 h) and (Cetuximab-TCO 48 h/99mTc-HYNIC-Polypeptide-PEG11-Tz 6 h) imagings was performed to show the effect of the two Tz-radioligands with different excretion pathway on tumor imaging. Results: 99mTc-HYNIC-Polypeptide-PEG11-Tz showed favorable in vitro stability and rapid blood clearance in mice. SEC-HPLC revealed almost complete reaction between Cetuximab-TCO and 99mTc-HYNIC-Polypeptide-PEG11-Tz in vitro, with the 8:1 Tz-to-mAb reaction providing a conversion yield of 87.83 ± 3.27%. The biodistribution and imaging of 99mTc-HYNIC-Polypeptide-PEG11-Tz demonstrated that the Tz-radioligand was cleared through kidneys. After allowing 24 h, 48 h and 72 h for accumulation of Cetuximab-TCO in HCT116 tumor, pretargeted biodistribution revealed the tumor-to-blood ratio was 0.83 ± 0.13, 1.40 ± 0.31, and 1.15 ± 0.21, respectively. Both pretargeted (Cetuximab-TCO 48 h/99mTc-HYNIC-PEG11-Tz 6 h) and (Cetuximab-TCO 48 h/99mTc-HYNIC-Polypeptide-PEG11-Tz 6 h) imaging delineated the HCT116 tumor clearly. However, pretargeted imaging strategy using Cetuximab-TCO/99mTc-HYNIC-Polypeptide-PEG11-Tz could be used for diagnosing CRC since the surplus unclicked 99mTc-HYNIC-Polypeptide-PEG11-Tz is cleared through urinary system and produces low abdominal uptake background. Conclusion: We developed a novel pretargeted imaging strategy (Cetuximab-TCO/99mTc-HYNIC-Polypeptide-PEG11-Tz) for imaging CRC since the surplus unclicked 99mTc-HYNIC-Polypeptide-PEG11-Tz produces low abdominal uptake background, which broadens the application scope of pretargeted imaging strategy.

Schisandrin B Attenuates Colitis-Associated Colorectal Cancer through SIRT1 Linked SMURF2 Signaling

2021 ◽  
pp. 1-17
Author(s):  
Zhichen Pu ◽  
Weiwei Zhang ◽  
Minhui Wang ◽  
Maodi Xu ◽  
Haitang Xie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Growth ◽  
Protein Expression ◽  
Hct116 Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Schisandrin B ◽  
In Vivo Models

Colon cancer, a common type of malignant tumor, seriously endangers human health. However, due to the relatively slow progress in diagnosis and treatment, the clinical therapeutic technology of colon cancer has not been substantially improved in the past three decades. The present study was designed to investigate the effects and involved mechanisms of schisandrin B in cell growth and metastasis of colon cancer. C57BL/6 mice received AOM and dextran sulfate sodium. Mice in treatment groups were gavaged with 3.75–30 mg/kg/day of schisandrin B. Transwell chamber migration, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunoprecipitation (IP) and immunofluorescence were conducted, and HCT116 cell line was employed in this study. Data showed that schisandrin B inhibited tumor number and tumor size in the AOD+DSS-induced colon cancer mouse model. Schisandrin B also inhibited cell proliferation and metastasis of colon cancer cells. We observed that schisandrin B induced SMURF2 protein expression and affected SIRT1 in vitro and in vivo. SMURF2 interacted with SIRT1 protein, and there was a negative correlation between SIRT1 and SMURF2 expressions in human colorectal cancer. The regulation of SMURF2 was involved in the anticancer effects of schisandrin B in both in vitro and in vivo models. In conclusion, the present study revealed that schisandrin B suppressed SIRT1 protein expression, and SIRT1 is negatively correlated with the induction of SMURF2, which inhibited cell growth and metastasis of colon cancer. Schisandrin B could be a leading compound, which will contribute to finding novel potential agents and therapeutic targets for colon cancer.

scholarly journals Design, Preparation, and Evaluation of a Novel 99mTcN Complex of Ciprofloxacin Xanthate as a Potential Bacterial Infection Imaging Agent

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5837
Author(s):  
Si’an Fang ◽  
Yuhao Jiang ◽  
Qianqian Gan ◽  
Qing Ruan ◽  
Di Xiao ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Radiochemical Purity ◽  
Binding Assay ◽  
Sterile Inflammation ◽  
Good Stability ◽  
Imaging Agent ◽  
Imaging Agents ◽  
Infection Imaging ◽  
Preparation And Evaluation

In order to seek novel technetium-99m bacterial infection imaging agents, a ciprofloxacin xanthate (CPF2XT) was synthesized and radiolabeled with [99mTcN]2+ core to obtain the 99mTcN-CPF2XT complex, which exhibited high radiochemical purity, hydrophilicity, and good stability in vitro. The bacteria binding assay indicated that 99mTcN-CPF2XT had specificity to bacteria. A study of biodistribution in mice showed that 99mTcN-CPF2XT had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses, indicating that it could distinguish bacterial infection from sterile inflammation. Compared to 99mTcN-CPFXDTC, the abscess/blood and abscess/muscle ratios of 99mTcN-CPF2XT were higher and the uptakes of 99mTcN-CPF2XT in the liver and lung were obviously decreased. The results suggested that 99mTcN-CPF2XT would be a potential bacterial infection imaging agent.

scholarly journals New CXCR4 Antagonist Peptide R (Pep R) Improves Standard Therapy in Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1952
Author(s):  
Crescenzo D’Alterio ◽  
Antonella Zannetti ◽  
Anna Maria Trotta ◽  
Caterina Ieranò ◽  
Maria Napolitano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Growth ◽  
Standard Therapy ◽  
Hct116 Cell ◽  
Human Colon ◽  
Chemotherapeutic Agents ◽  
Cxcr4 Antagonist ◽  
Human Colon Cancer

The chemokine receptor CXCR4 is overexpressed and functional in colorectal cancer. To investigate the role of CXCR4 antagonism in potentiating colon cancer standard therapy, the new peptide CXCR4 antagonist Peptide R (Pep R) was employed. Human colon cancer HCT116 xenograft-bearing mice were treated with chemotherapeutic agents (CT) 5-Fluorouracil (5FU) and oxaliplatin (OX) or 5FU and radio chemotherapy (RT-CT) in the presence of Pep R. After two weeks, CT plus Pep R reduced by 4-fold the relative tumor volume (RTV) as compared to 2- and 1.6-fold reductions induced, respectively, by CT and Pep R. In vitro Pep R addition to CT/RT-CT impaired HCT116 cell growth and further reduced HCT116 and HT29 clonal capability. Thus, the hypothesis that Pep R could target the epithelial mesenchyme transition (EMT) process was evaluated. While CT decreased ECAD and increased ZEB-1 and CD90 expression, the addition of Pep R restored the pretreatment expression. In HCT116 and HT29 cells, CT/RT-CT induced a population of CD133+CXCR4+ cells, supposedly a stem-resistant cancer cell population, while Pep R reduced it. Taken together, the results showed that targeting CXCR4 ameliorates the effect of treatment in colon cancer through inhibition of cell growth and reversal of EMT treatment-induced markers, supporting further clinical studies.

Preparation and Preliminary Evaluation of 68 Ga-Acridine: An Attempt to Study the Potential of Radiolabeled DNA Intercalator as a PET Radiotracer for Tumor Imaging

2020 ◽  
Vol 20 (13) ◽  
pp. 1538-1547 ◽  
Author(s):  
Subhajit Ghosh ◽  
Tapas Das ◽  
Shishu K. Suman ◽  
Haladhar D. Sarma ◽  
Ashutosh Dash
Keyword(s):  
Radiochemical Purity ◽  
Tumor Imaging ◽  
Raji Cell ◽  
Biological Behavior ◽  
Preliminary Evaluation ◽  
Dna Intercalator ◽  
Tumor Accumulation ◽  
The Stability

Introduction: Acridine is a well-known DNA intercalator and thereby gets easily inserted within DNA. As uncontrolled rapid cell division is one of the primary characteristics of the tumors, it is expected that acridine or its suitable derivatives will have preferential accumulation in the tumorous lesions. Therefore, an attempt was made to radiolabel an acridine derivative with 68Ga and study the potential of the 68Ga-acridine complex as a PET agent for tumor imaging. Methods: 9-aminoacridine was coupled with p-NCS-benzyl-DOTA to render it suitable for labeling with 68Ga. The purified acridine-DOTA conjugate was radiolabeled with 68Ga, eluted from a 68Ge/68Ga radionuclide generator. Various radiolabeling parameters were optimized and the stability of the radiolabeled preparation was studied. The biological behavior of the 68Ga-acridine complex was studied both in vitro and in vivo using Raji cell line and fibrosarcoma tumor bearing Swiss mice, respectively. Results: 68Ga-acridine complex was obtained with ~100% radiochemical purity under the optimized reaction conditions involving incubation of 2mg/mL of ligand at 100°C for 30 minutes. The complex maintained a radiochemical purity of >95% in normal saline and >65% in human blood serum at 3h post-incubation. In vitro cellular study showed (3.2±0.1)% uptake of the radiotracer in the Raji cells. Biodistribution study revealed significant tumor accumulation [(11.41±0.41)% injected activity in per gram] of the radiotracer within 1h postadministration along with uptake in other non-target organs such as, blood, liver, GIT kidney etc. Conclusion: The present study indicates the potential of 68Ga-acridine as a PET agent for imaging of tumorous lesions. However, further detailed evaluation of the agent is warranted to explore its actual potential.

scholarly journals Eduscho Coffee Extract Effectively Inhibits the Formation of Amyloid-like Fibrils by Trypsin in Aqueous Ethanol

2018 ◽  
Vol 13 (12) ◽  
pp. 1934578X1801301 ◽  
Author(s):  
Phanindra Babu Kasi ◽  
Attila Borics ◽  
Kinga Molnár ◽  
Lajos László ◽  
Márta Kotormán
Keyword(s):  
Binding Assay ◽  
Phenolic Content ◽  
Aqueous Ethanol ◽  
Inhibitory Effect ◽  
Size Exclusion ◽  
Total Phenolic ◽  
Transmission Electron ◽  
Oligomeric Form ◽  
Exclusion Chromatography

In this work we used an in vitro trypsin aggregation model to show that certain commercial coffee extracts can inhibit protein aggregation. Aggregation experiments were performed using several spectroscopic methods and a dye binding assay, such as turbidity, Congo red (CR) and electronic circular dichroism (ECD), that was further supported by transmission electron microscopy (TEM). A correlation was found between the anti-aggregation properties and the total phenolic content of the coffee extracts. The results revealed that the greatest effect was exerted by the Eduscho coffee extract. It was found that the inhibitory effect of this extract was concentration dependent. Using size exclusion chromatography, we demonstrated that the inhibitory effect of the Eduscho coffee extract on the formation of amyloid-like fibrils was due to its capacity to stabilize the oligomeric form of the protein.

Colon Available Bioactive Compounds Exhibits Anticancer Effect on In-Vitro Model of Colorectal Cancer

2021 ◽  
Author(s):  
Poounima Patil ◽  
Suresh Killedar
Keyword(s):  
Colorectal Cancer ◽  
Gallic Acid ◽  
Hct116 Cell ◽  
Chitosan Nanoparticles ◽  
Entrapment Efficiency ◽  
Spectroscopic Techniques ◽  
X Ray Diffraction ◽  
Hct 116 ◽  
Vitro Model

The current work was addressed to characterize gallic acid from amla fruit and quercetin from peels of pomegranate fruit and formulated into Chitosan (CS) nanoparticles and to evaluate their cytotoxicity towards human colorectal cancer (HCT 116) cell lines. Identification of the biomolecules was performed by chromatographic and spectroscopic techniques and characterization of gallic acid and quercetin loaded chitosan nanoparticles carried out by using FT-IR, X- ray diffraction, entrapment efficiency and loading content confirmed successful encapsulation of biomolecules into nanoparticles. In vitro drug release studies done by using simulated fluids at various pH (1.2, 4.5, 7.5, and 7.0) to mimic the GIT tract and achieved drug releases 77.56% for gallic acid 79.06% for quercetin at 24 hr. in a sustained manner. The human HCT116 cell line by MTT assay results inferred that the synthesized CS nanoparticles demonstrated shows more effective antiproliferative potential with IC50 value of 36.17 ug/ml than polyherbal extract 60.32ug/ml.

scholarly journals Antibody-Based Targeting of Cell Surface GRP94 Specifically Inhibits Cetuximab-Resistant Colorectal Cancer Growth

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 681
Author(s):  
Mee Hyun Jeoung ◽  
Taek-Keun Kim ◽  
Ji Woong Kim ◽  
Yea Bin Cho ◽  
Hee Jun Na ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cell Surface ◽  
Hct116 Cell ◽  
Target Antigen ◽  
Human Antibody ◽  
Severe Toxicity ◽  
Phage Display Technology ◽  
Novel Therapeutic

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Cetuximab, a human/mouse chimeric monoclonal antibody, is effective in a limited number of CRC patients because of cetuximab resistance. This study aimed to identify novel therapeutic targets in cetuximab-resistant CRC in order to improve clinical outcomes. Through phage display technology, we isolated a fully human antibody strongly binding to the cetuximab-resistant HCT116 cell surface and identified the target antigen as glucose-regulated protein 94 (GRP94) using proteomic analysis. Short interfering RNA-mediated GRP94 knockdown showed that GRP94 plays a key role in HCT116 cell growth. In vitro functional studies revealed that the GRP94-blocking antibody we developed strongly inhibits the growth of various cetuximab-resistant CRC cell lines. We also demonstrated that GRP94 immunoglobulin G monotherapy significantly reduces HCT116 cell growth more potently compared to cetuximab, without severe toxicity in vivo. Therefore, cell surface GRP94 might be a potential novel therapeutic target in cetuximab-resistant CRC, and antibody-based targeting of GRP94 might be an effective strategy to suppress GRP94-expressing cetuximab-resistant CRC.

scholarly journals Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 681 ◽  
Author(s):  
Francesca Sensi ◽  
Edoardo D’Angelo ◽  
Martina Piccoli ◽  
Piero Pavan ◽  
Francesca Mastrotto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
3D Model ◽  
Hct116 Cell ◽  
Unmet Need ◽  
Patient Specific ◽  
Original Structure ◽  
Preclinical Model ◽  
Chemosensitivity Test

Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (Danio rerio) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC50) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC50 fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment.

Synthesis and Biological Evaluation of 7-(2-Chlorophenylamino)-5-((2- [18F]fluoro-ethyoxy)methyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile as PET Tumor Imaging Agent

2012 ◽  
Vol 67 (8) ◽  
pp. 827-834 ◽  
Author(s):  
Jingli Xu ◽  
Hang Liu ◽  
Guixia Li ◽  
Yong He ◽  
Rui Ding ◽  
...  
Keyword(s):  
Radiochemical Purity ◽  
Tumor Imaging ◽  
Chemical Yield ◽  
Biological Evaluation ◽  
Pyrimidine Derivative ◽  
Emission Tomography ◽  
Positron Emission ◽  
Radio Tracer ◽  
Synthesis And Biological Evaluation

An 18F-labeled pyrazolo[1,5-a]pyrimidine derivative, 7-(2-chlorophenylamino)-5-((2-[18F] fluoroethyoxy)methyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile ([18F]5), has been designed and prepared as a radio tracer candidate for tumor detection with positron emission tomography (PET). The desired product [18F]5was synthesized by nucleophilic substitution of the corresponding tosylated precursor with [18F]KF=Kryptofix 2.2.2 and potassium carbonate in anhydrous DMF at 100 °C for 20 min followed by purification with HPLC. The radiochemical purity was >98%, and the radio-chemical yield was 25% (decay-uncorrected). Compound [18F]5was very stable in vitro. The biodistribution study in mice bearing S180 tumors demonstrated that [18F]5had a rapid and prolonged accumulation in tumors with moderate washout from other tissues

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