Da Pieve, C., Allott, L., Martins, C.D., Vardon, A., Ciobota, D.M., Kramer-Marek, G. & Smith, G.
(2016). Efficient [(18)F]AlF Radiolabeling of ZHER3:8698 Affibody Molecule for Imaging of HER3 Positive Tumors. Bioconjug chem,
The human epidermal growth factor receptor 3 (HER3) is overexpressed in several cancers, being linked to a more resistant phenotype and hence leading to poor patient prognosis. Imaging HER3 is challenging owing to the modest receptor number (<50000 receptors/cell) in overexpressing cancer cells. Therefore, to image HER3 in vivo, high target affinity PET probes need to be developed. This work describes two different [(18)F]AlF radiolabeling strategies of the ZHER3:8698 affibody molecule specifically targeting HER3. The one-pot radiolabeling of ZHER3:8698 performed at 100 °C and using 1,4,7-triazanonane-1,4,7-triacetate (NOTA) as chelator resulted in radiolabeled products with variable purity attributed to radioconjugate thermolysis. An alternative approach based on the inverse electron demand Diels-Alder (IEDDA) reaction between a novel tetrazine functionalized 1,4,7-triazacyclononane-1,4-diacetate (NODA) chelator and the trans-cyclooctene (TCO) functionalized affibody molecule was also investigated. This method enabled the radiolabeling of the protein at room temperature. The [(18)F]AlF-NOTA-ZHER3:8698 and [(18)F]AlF-NODA-ZHER3:8698 conjugates showed a specific uptake at 1 h after injection in high HER3-expressing MCF-7 tumors of 4.36 ± 0.92% ID/g and 4.96 ± 0.65% ID/g, respectively. The current results are encouraging for further investigation of [(18)F]AlF-NOTA-ZHER3:8698 as a HER3 imaging agent..
Allott, L., Smith, G., Aboagye, E.O. & Carroll, L.
(2015). PET Imaging of Steroid Hormone Receptor Expression. Molecular imaging,
Haywood, T., Kealey, S., Sánchez-Cabezas, S., Hall, J.J., Allott, L., Smith, G., Plisson, C. & Miller, P.W.
(2015). Carbon-11 Radiolabelling of Organosulfur Compounds:11C Synthesis of the Progesterone Receptor Agonist Tanaproget. Chemistry - a european journal,
Pacelli, A., Greenman, J., Cawthorne, C. & Smith, G.
(2014). Imaging COX-2 expression in cancer using PET/SPECT radioligands: current status and future directions. Journal of labelled compounds & radiopharmaceuticals,
Nguyen, Q.-., Lavdas, I., Gubbins, J., Smith, G., Fortt, R., Carroll, L.S., Graham, M.A. & Aboagye, E.O.
(2013). Temporal and spatial evolution of therapy-induced tumor apoptosis detected by caspase-3-selective molecular imaging. Clin cancer res,
PURPOSE: Induction of apoptosis in tumors is considered a desired goal of anticancer therapy. We investigated whether the dynamic temporal and spatial evolution of apoptosis in response to cytotoxic and mechanism-based therapeutics could be detected noninvasively by the caspase-3 radiotracer [(18)F]ICMT-11 and positron emission tomography (PET). EXPERIMENTAL DESIGN: The effects of a single dose of the alkylating agent cyclophosphamide (CPA or 4-hydroperoxycyclophosphamide), or the mechanism-based small molecule SMAC mimetic birinapant on caspase-3 activation was assessed in vitro and by [(18)F]ICMT-11-PET in mice bearing 38C13 B-cell lymphoma, HCT116 colon carcinoma, or MDA-MB-231 breast adenocarcinoma tumors. Ex vivo analysis of caspase-3 was compared to the in vivo PET imaging data. RESULTS: Drug treatment increased the mean [(18)F]ICMT-11 tumor uptake with a peak at 24 hours for CPA (40 mg/kg; AUC40-60: 8.04 ± 1.33 and 16.05 ± 3.35 %ID/mL × min at baseline and 24 hours, respectively) and 6 hours for birinapant (15 mg/kg; AUC40-60: 20.29 ± 0.82 and 31.07 ± 5.66 %ID/mL × min, at baseline and 6 hours, respectively). Voxel-based spatiotemporal analysis of tumor-intrinsic heterogeneity suggested that discrete pockets of caspase-3 activation could be detected by [(18)F]ICMT-11. Increased tumor [(18)F]ICMT-11 uptake was associated with caspase-3 activation measured ex vivo, and early radiotracer uptake predicted apoptosis, distinct from the glucose metabolism with [(18)F]fluorodeoxyglucose-PET, which depicted continuous loss of cell viability. CONCLUSION: The proapoptotic effects of CPA and birinapant resulted in a time-dependent increase in [(18)F]ICMT-11 uptake detected by PET. [(18)F]ICMT-11-PET holds promise as a noninvasive pharmacodynamic biomarker of caspase-3-associated apoptosis in tumors..
Kaliszczak, M., Patel, H., Kroll, S.H., Carroll, L., Smith, G., Delaney, S., Heathcote, D.A., Bondke, A., Fuchter, M.J., Coombes, R.C., et al.
(2013). Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance. Br j cancer,
BACKGROUND: Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy. METHODS: We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy. RESULTS: We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å(2)) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively. CONCLUSION: We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer..
Tietz, O., Kamaly, N., Smith, G., Shamsaei, E., Bhakoo, K.K., Long, N.J. & Aboagye, E.O.
(2013). Design, synthesis and in vitro characterization of fluorescent and paramagnetic CXCR4-targeted imaging agents. Am j nucl med mol imaging,
The G-protein coupled C-X-C chemokine receptor type 4 (CXCR4) is highly overexpressed in a range of cancers and is therefore an excellent biomarker for cancer imaging. To this end targeted iron oxide nanoparticles were developed and utilised for in vitro imaging of MDA-MB-231 breast cancer cells overexpressing the CXCR4 receptor. Nanoparticles comprising an iron oxide core, encapsulated in a stabilising epichlorohydrin crossed-linked dextran polymer, were conjugated to a cyclopentapeptide with affinity to the CXCR4 receptor. The particles were characterized for their size, surface charge and r2 relaxivity at 4.7 T. MR imaging of the CXCR4 receptor with targeted iron oxide nanoparticles revealed an approximately 3-fold increase in T2 signal enhancement of MDA-MB-231 cells compared to non-targeted controls. Prussian blue staining of labeled MDA-MB-231 cells revealed darker and more intense staining of the cellular membrane. This study demonstrates the potential of targeted iron oxide nanoparticles for the imaging of the CXCR4 receptor by magnetic resonance imaging (MRI). .
Nguyen, Q.-., Challapalli, A., Smith, G., Fortt, R., Aboagye, E.O. & Consortium, Q.-.
(2012). Imaging apoptosis with positron emission tomography: 'Bench to bedside' development of the caspase-3/7 specific radiotracer [F-18]ICMT-11. European journal of cancer,
Aberg, O., Pisaneschi, F., Smith, G., Nguyen, Q.-., Stevens, E. & Aboagye, E.O.
(2012). F-18-labelling of a cyclic pentapeptide inhibitor of the chemokine receptor CXCR4. Journal of fluorine chemistry,
Smith, G., Sala, R., Carroll, L., Behan, K., Glaser, M., Robins, E., Nguyen, Q.-. & Aboagye, E.O.
(2012). Synthesis and evaluation of nucleoside radiotracers for imaging proliferation. Nucl med biol,
INTRODUCTION: Uncontrolled proliferation is a fundamental characteristic of cancer, and consequently, imaging of tumor proliferative status finds interest clinically both as a diagnostic tool and for evaluation of response to treatment. Positron emission tomography (PET) radiotracers based on a nucleoside core, such as 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT), have been extensively studied for this purpose. However, [18F]FLT suffers from poor DNA incorporation leading to occasional poor correlation of [18F]FLT tumor uptake with other proliferation indicators such as Ki-67 immunostaining. METHODS: N3-((1-(2-[18F]fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)thymidine ([18F]2) and N3-((1-(2-[18F]fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-4'-thio-β-thymidine ([18F]3) were synthesized by click chemistry from [18F]fluoroethyl azide and by direct nucleophilic substitution of a tosylate precursor. Metabolic stability and phosphorylation potential of the radiotracers were evaluated in vitro and compared to [18F]FLT. Further, metabolic stability and biodistribution analysis of [18F]2 and [18F]3 were evaluated in vivo. RESULTS: Stable isotope standards and radiochemistry precursors were synthesized by modification of existing literature procedures. [18F]2 and [18F]3 were synthesized in a radiochemical yield of 8%-12% (end of synthesis, non-decay corrected). Both nucleosides were stable to metabolic degradation by thymidine phosphorylase, and in vivo stability analysis showed only one metabolite for [18F]3. No phosphorylation of [18F]2 could be detected in HCT116 cell homogenates, and in the same assay, only minor (∼8%) phosphorylation of [18F]3 was observed. Biodistribution in Balb/c mice indicated rapid clearance for [18F]2 and [18F]3 to a lesser extent. CONCLUSIONS: The favorable biodistribution and metabolic profile of [18F]3 warrant further investigation as a next-generation PET proliferation marker..
Fortt, R., Smith, G., Awais, R.O., Luthra, S.K. & Aboagye, E.O.
(2012). Automated GMP Synthesis of [F-18]ICMT-11 for In Vivo Imaging of Caspase-3 Activity. Nuclear medicine and biology,
Smith, G., Carroll, L. & Aboagye, E.O.
(2012). New Frontiers in the Design and Synthesis of Imaging Probes for PET Oncology: Current Challenges and Future Directions. Molecular imaging and biology,
Witney, T.H., Alam, I.S., Turton, D.R., Smith, G., Carroll, L., Brickute, D., Twyman, F.J., Nguyen, Q.-., Tomasi, G., Awais, R.O., et al.
(2012). Evaluation of Deuterated F-18- and C-11-Labeled Choline Analogs for Cancer Detection by Positron Emission Tomography. Clinical cancer research,
Evans, H.L., Slade, R.L., Carroll, L., Smith, G., Nguyen, Q.-., Iddon, L., Kamaly, N., Stöckmann, H., Leeper, F.J., Aboagye, E.O., et al.
(2012). Copper-free click--a promising tool for pre-targeted PET imaging. Chem commun (camb),
The copper-free click (CFC) reaction has been evaluated for its potential application to in vivo pre-targeting for PET imaging. A promising biodistribution profile is demonstrated when employing [(18)F]2-fluoroethylazide ([(18)F]1) and optimisation of the CFC reaction with a series of cyclooctynes shows that reactions proceed efficiently with tantalizing opportunities for application-specific tuning..
Smith, G., Zhao, Y., Leyton, J., Shan, B., Nguyen, Q.-., Perumal, M., Turton, D., Årstad, E., Luthra, S.K., Robins, E.G., et al.
(2011). Radiosynthesis and pre-clinical evaluation of [(18)F]fluoro-[1,2-(2)H(4)]choline. Nucl med biol,
INTRODUCTION: Choline radiotracers are widely used for clinical PET diagnosis in oncology. [(11)C]Choline finds particular utility in the imaging of brain and prostate tumor metabolic status, where 2-[(18)F]fluoro-2-deoxy-D-glucose ('FDG') shows high background uptake. More recently we have extended the clinical utility of [(11)C]choline to breast cancer where radiotracer uptake correlates with tumor aggressiveness (grade). In the present study, a new choline analog, [(18)F]fluoro-[1,2-(2)H(4)]choline, was synthesized and evaluated as a potential PET imaging probe. METHODS: [(18)F]Fluorocholine, [(18)F]fluoro-[1-(2)H(2)]choline and [(18)F]fluoro-[1,2-(2)H(4)]choline were synthesized by alkylation of the relevant precursor with [(18)F]fluorobromomethane or [(18)F]fluoromethyl tosylate. Radiosynthesis of [(18)F]fluoromethyl tosylate required extensive modification of the existing method. [(18)F]Fluorocholine and [(18)F]fluoro-[1,2-(2)H(4)]choline were then subjected to in vitro oxidative stability analysis in a chemical oxidation model using potassium permanganate and an enzymatic model using choline oxidase. The two radiotracers, together with the corresponding di-deuterated compound, [(18)F]fluoro-[1-(2)H(2)]choline, were then evaluated in vivo in a time-course biodistribution study in HCT-116 tumor-bearing mice. RESULTS: Alkylation with [(18)F]fluoromethyl tosylate proved to be the most reliable radiosynthetic route. Stability models indicate that [(18)F]fluoro-[1,2-(2)H(4)]choline possesses increased chemical and enzymatic (choline oxidase) oxidative stability relative to [(18)F]fluorocholine. The distribution of the three radiotracers, [(18)F]fluorocholine, [(18)F]fluoro-[1-(2)H(2)]choline and [(18)F]fluoro-[1,2-(2)H(4)]choline, showed a similar uptake profile in most organs. Crucially, tumor uptake of [(18)F]fluoro-[1,2-(2)H(4)]choline was significantly increased at late time points compared to [(18)F]fluorocholine and [(18)F]fluoro-[1-(2)H(2)]choline. CONCLUSIONS: Stability analysis and biodistribution suggest that [(18)F]fluoro-[1,2-(2)H(4)]choline warrants further in vivo investigation as a PET probe of choline metabolism..
Glaser, M., Goggi, J., Smith, G., Morrison, M., Luthra, S.K., Robins, E. & Aboagye, E.O.
(2011). Improved radiosynthesis of the apoptosis marker F-18-ICMT11 including biological evaluation. Bioorganic & medicinal chemistry letters,
Smith, G., Fortt, R., Awais, R., Carroll, L., Abrahams, J., Black, A., Goggi, J., Glaser, M., Robins, E., Morrison, M., et al.
(2011). Automation of [F-18]ICMT-11 for imaging apoptosis. Journal of labelled compounds & radiopharmaceuticals,
Smith, G., Carroll, L., Sala, R., Leyton, J., Quang-de, N., Behan, K., Twyman, F., Robins, E. & Aboagye, E.
(2011). Synthesis and evaluation of nucleoside radiotracers for imaging tumour proliferation. Journal of labelled compounds & radiopharmaceuticals,
Aberg, O., Stevens, E., Pisaneschi, F., Smith, G. & Aboagye, E.
(2011). Cyclic pentapetide conjugates as potential CXCR4 imaging agents. Journal of labelled compounds & radiopharmaceuticals,
Pisaneschi, F., Nguyen, Q.-., Shamsaei, E., Glaser, M., Robins, E., Kaliszczak, M., Smith, G., Spivey, A.C. & Aboagye, E.O.
(2010). Development of a new epidermal growth factor receptor positron emission tomography imaging agent based on the 3-cyanoquinoline core: synthesis and biological evaluation. Bioorg med chem,
The epidermal growth factor receptor (EGFR/c-ErbB1/HER1) is overexpressed in many cancers including breast, ovarian, endometrial, and non-small cell lung cancer. An EGFR specific imaging agent could facilitate clinical evaluation of primary tumors and/or metastases. To achieve this goal we designed and synthesized a small array of fluorine containing compounds based on a 3-cyanoquinoline core. A lead compound, 16, incorporating 2'-fluoroethyl-1,2,3-triazole was selected for evaluation as a radioligand based on its high affinity for EGFR kinase (IC50=1.81+/-0.18 nM), good cellular potency (IC50=21.97+/-9.06 nM), low lipophilicity and good metabolic stability. 'Click' labeling afforded [18F]16 in 37.0+/-3.6% decay corrected radiochemical yield based on azide [18F]14 and 7% end of synthesis (EOS) yield from aqueous fluoride. Compound [18F]16 was obtained with >99% radiochemical purity in a total synthesis time of 3 h. The compound showed good stability in vivo and a fourfold higher uptake in high EGFR expressing A431 tumor xenografts compared to low EGFR expressing HCT116 tumor xenografts. Furthermore, the radiotracer could be visualized in A431 tumor bearing mice by small animal PET imaging. Compound [18F]16 therefore constitutes a promising radiotracer for further evaluation for imaging of EGFR status..
Leyton, J., Smith, G., Zhao, Y., Perumal, M., Nguyen, Q.-., Robins, E., Arstad, E. & Aboagye, E.O.
(2009). [F-18]Fluoromethyl-[1,2-H-2(4)]-Choline: A Novel Radiotracer for Imaging Choline Metabolism in Tumors by Positron Emission Tomography. Cancer research,
Smith, G., Nguyen, Q.-. & Aboagye, E.O.
(2009). Translational imaging of apoptosis. Anticancer agents med chem,
Deregulated apoptosis is involved in several diseases including myocardial infarction, ischemia and neurodegenerative disorders, which are characterized by excessive apoptosis. In contrast, resistance to apoptosis is defined as one of the hallmarks of cancer. It therefore follows that strategies that enable the quantitative detection of apoptosis modulation in vivo would be of enormous benefit in the clinic for diagnosis and patient management (evaluation of response to treatment). In addition, such strategies could be used to evaluate the efficacy of novel therapeutics along their development process. During the development of novel therapeutics it would be necessary to evaluate drug efficacy in vitro and then in experimental animal models and, ultimately, in clinical trials. Currently there is no one single probe that is suitable for imaging apoptosis at every stage of evaluation, necessitating a switch between probe types during the development process. This has key implications for the quality and reproducibility of the data obtained. The present review summarizes the development of new apoptosis detecting probes that have the potential for bridging different stages of the evaluation process such that accurate, translational apoptosis imaging data are obtained..
Nguyen, Q.-., Smith, G., Glaser, M., Perumal, M., Arstad, E. & Aboagye, E.O.
(2009). Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-3/7 specific [18F]-labeled isatin sulfonamide. Proc natl acad sci u s a,
Of the molecular biochemical alterations that occur during apoptosis, activation of caspases, notably caspase-3, is probably the most attractive for developing specific in vivo molecular imaging probes. We recently designed a library of isatin-5 sulfonamides and selected [18F]ICMT-11 for further evaluation on the basis of subnanomolar affinity for activated capsase-3, high metabolic stability, and facile radiolabeling. In this present study, we have demonstrated that [18F]ICMT-11 binds to a range of drug-induced apoptotic cancer cells in vitro and to 38C13 murine lymphoma xenografts in vivo by up to 2-fold at 24 h posttreatment compared to vehicle treatment. We further demonstrated that the increased signal intensity in tumors after drug treatment, detected by whole body in vivo microPET imaging, was associated with increased apoptosis. In summary, we have characterized [18F]ICMT-11 as a caspase-3/7 specific PET imaging radiotracer for the assessment of tumor apoptosis that could find utility in anticancer drug development and the monitoring of early responses to therapy..
Smith, G., Nguyen, Q., Glaser, M., Perumal, M., Arstad, E. & Aboagye, E.
(2009). DEVELOPMENT OF AN ISATIN-5-SULFONAMIDE BASED PET PROBE FOR IMAGING APOPTOSIS IN VIVO. Journal of labelled compounds & radiopharmaceuticals,
Leyton, J., Smith, G., Lees, M., Perumal, M., Nguyen, Q.D., Aigbirhio, F.I., Golovko, O., He, Q.M., Workman, P. & Aboagye, E.O., et al.
(2008). Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901. Mol cancer ther,
The mitogenic extracellular kinase 1/2 (MEK1/2) inhibitor, PD0325901, has potent activity in a number of cancer cell types in vitro. In SKMEL-28 human melanoma cells (BRAF mutant), the drug rapidly decreased phosphorylated extracellular signal-regulated kinase 1/2, cyclin 131, and thymidine kinase 1 protein levels. We investigated if 3'-deoxy-3'-[F-18]fluorothymidine-positron emission tomography ([F-18]FLT-PET) could be used to image changes in cell proliferation following MEK1/2 inhibition in vivo. Mice bearing SKMEL-28 and human colon cancer HCT116 (K-RAS mutant) xenografts were treated daily with PD0325901 at 25 mg/kg and imaged by dynamic [18F]FLT-PET after 1 and 10 days of initiating treatment. The drug decreased tumor [F-18]FLT uptake after 1 and 10 days of treatment compared with control animals. The normalized (maximal) [F-18]FLT uptake in SKMEL-28 xenografts (at 60 minutes; NUVmax) after 1 day of vehicle or PD0325901 therapy was 1.81 +/- 0.18 versus 1.23 +/- 0.10, respectively (P = 0.03). In this model, NUVmax after 10 days was 2.07 +/- 0.40 versus 1.08 +/- 0.14, respectively (P = 0.03). The corresponding values for HCT116 tumors were 2.30 +/- 0.84 versus 1.88 +/- 0.36 (P = 0.045) after 1 day, and 1.97 +/- 0.13 versus 1.00 +/- 0.03 (P = 0.03) after 10 days. Similar changes were found for other [F-18]FLT retention variables. The drug decreased phosphorylated extracellular signal-regulated kinase 1/2, cyclin D1, and thymidine kinase 1 protein. Tumor [F-18]FLT-PET variables correlated with proliferation as measured by Ki67 labeling index (r >= 0.6; P >= 0.003). In summary, [F-18]FLT-PET is a sensitive imaging biomarker for detecting the antiproliferative effect of MEK1/2 inhibition by PD0325901..
Smith, G., Glaser, M., Perumal, M., Nguyen, Q.-., Shan, B., Arstad, E. & Aboagye, E.O.
(2008). Design, synthesis, and biological characterization of a caspase 3/7 selective isatin labeled with 2-[18F]fluoroethylazide. J med chem,
Imaging of programmed cell death (apoptosis) is important in the assessment of therapeutic response in oncology and for diagnosis in cardiac and neurodegenerative disorders. The executioner caspases 3 and 7 ultimately effect cellular death, thus providing selective molecular targets for in vivo quantification of apoptosis. To realize this potential, we aimed to develop 18F-labeled isatin sulfonamides with high metabolic stability and moderate lipophilicity while retaining selectivity and affinity for caspase 3/7. A small library of isatins modified with fluorinated aromatic groups and heterocycles was synthesized. A lead compound incorporating 2'-fluoroethyl-1,2,3-triazole was identified with subnanomolar affinity for caspase 3. "Click labeling" provided the 18F-labeled tracer in 65 +/- 6% decay-corrected radiochemical yield from 2-[18F]fluoroethylazide. The compound showed high stability in vivo with rapid uptake and elimination in healthy tissues and tumor. The novel 18F-labeled isatin is a candidate radiotracer for further preclinical evaluation for imaging of apoptosis..
Udemba, A., Smith, G., Nguyen, Q.-., Kaliszczak, M., Carroll, L., Fortt, R., Fuchter, M.J. & Aboagye, E.O.
Design, synthesis and initial characterisation of a radiolabelled [18F]pyrimidoindolone probe for detecting activated caspase-3/7. Organic & biomolecular chemistry,
Evasion of apoptosis is one of the six initially proposed hallmarks of cancer, and as such, a method to detect apoptosis in a tumour would be of considerable interest in both clinical trials of new cancer therapeutics, as well as for routine patient management.
Merchant, S., Allott, L., Carroll, L., Tittrea, V., Kealey, S., Witney, T.H., Miller, P.W., Smith, G. & Aboagye, E.O.
Synthesis and pre-clinical evaluation of a [18F]fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression. Rsc advances,
This work features the synthesis and biological evaluation of a novel fluorinated derivative of tanaproget and a carbon-11 labelled analogue, a high affinity non-steroidal PR ligand, as a possible candidate for imaging PR expressionin vivo.
An alternative synthesis of Vandetanib (Caprelsa™) viavia a microwave accelerated Dimroth rearrangement. Tetrahedron letters,
Evaluation of DFO-HOPO as an octadentate chelator for zirconium-89. Chemical communications,
A practical microwave method for the synthesis of fluoromethy 4-methylbenzenesulfonate in tert-amyl alcohol. Tetrahedron letters,
Smith, G., King, A., Doepner, A., Turton, D., Ciobota, D., Da Pieve, C., Wong Te Fong, A.-., Kramer-Marek, G. & Chung, Y.
Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure. Organic and biomolecular chemistry,