J. A. H. Inkster, S. Zhang, V. Akurathi, A. Belanger, S. Dubey, S. T. Treves, A. B. Packard
New chemical and radiochemical syntheses are described for the preparation of [18F]Rho6G-DEG-F, an 18F-labeled analogue of the fluorescent dye rhodamine 6G, which has shown promise as myocardidal perfusion imaging agent. Tosylated precursors of [18F]Rho6G-DEG-F amenable to 18F-labeling were obtained either through a two-step synthesis from rhodamine 6G lactone (33% yield), or in one step from rhodamine 575 (64% yield), then purified by preparative C18 chromatography. Manual synthesis of [18F]Rho6G-DEG-F was achieved in a single radiochemical step from either the tosylate salt or the tosylate/formate double salt in DMSO under standard nucleophillic aliphatic 18F-fluorination conditions (K[18F]F/K2CO3/Kryptofix 2.2.2.). Incorporation of the [18F]F− was found to be satisfactory (≥34% by TLC), despite the protic character of the precursor molecules. [18F]Rho6G-DEG-F was manually synthesized in final decay-corrected radiochemical yields of 11–26% (tosylate salt) and 9–21% (tosylate/formate double salt). The protocol was transferred to an automated synthesis unit, where the product was obtained in 3–9% radiochemical yield (n = 3) decay corrected to start-of-synthesis, >99% radiochemical purity, and a molar activity of 122–267 GBq μmol−1 (3.3–7.2 Ci μmol−1).
The MS analysis was carried out using Advion Expression® CMS.
Additi Roy Chowdhury, Biswajit Gopal Roy, Saibal Jana, Thomas Weyhermuller, Priyata Banerjee
Novel colorimetric hydrazine-functionalized Schiff base chemoreceptor [N1N3bis(perfluorobenzylidene)isophthalahydrazide] NBPBIH has been prepared for selective detection of F−. In this receptor more NH and CN units are incorporated for better colorimetric responses as compared to systems having lesser number of such units. NBPBIH turns from colorless to dark yellow on exposure to F−. The detection event is well supported by UV–vis, fluorescence, 1H and 19F-NMR like spectrophotometric and cyclic voltammetric studies in DMSO because of enhanced fluorescence responses, higher Stokes shift value and for its less toxic nature compared to other solvents. Quenching of fluorescence is explained with photoinduced electron transfer mechanism (PET). The binding constant of NBPBIH with F− is around 0.84 × 105 M−1 and limit of detection of F− is found 1.42 × 10−5 M. Our concern is also to address fluorosis: an issue related to global health problem, affecting millions of common people. It is noteworthy that the existing diagnostic and treatment options are of huge expenses. As an artefact, chemoreceptor assisted simple prototype for detecting excessive fluoride in sample solution has been designed and developed which has potential and good prospect to be applied as a low cost affordable diagnostic kit for fluorosis in largely affected countries like China, India and several others.
The MS analysis was carried out using Advion Expression® CMS ESI.
A: My research at the Biomedical Research Imaging Center (BRIC) focuses on the development and validation of novel radiolabeling methods and multimodality molecular imaging probes for various diseases, including cancer, diabetes, neuro-disease, and cardio vasculature disease. To be more specific, the major efforts of my current research include: 1) developing novel radiochemistry for cancer diagnosis, neuroimaging, cardiac imaging, diabetic research, drug discovery and development, and targeted radionuclide therapy; 2) developing multimodality molecular imaging agents; 3) developing novel nanotechnology and studying its biomedical applications; 4) developing pre-targeted drug delivery system for cancer imaging and therapy; and 5) performing PET related translational research.
Q: WHAT WAS YOUR PREVIOUS WORK FLOW OR CHALLENGES?
A: Sometimes we have a reaction, and we do not know which peak contained the product, so we send the sample to the mass spectrometry facility to be analyzed. Additionally, there are times when we have 10-20 peaks, and it is impossible to collect them all to be sent.
Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?
A: The convenience of having a mass spectrometer in our laboratory means that we can increase working efficiencies by not waiting 2-3 days for results from the LC lab. The expression® CMS is a good system for routine analysis.
Q: TO WHOM WOULD YOU RECOMMEND THE EXPRESSION® CMS?
A: I recommend the expression® CMS to any traditional organic and radiochemistry laboratory. I am impressed by the smaller size and by how simple it is to operate. We were able to use it quickly.
A: As part of the Archibald research group our main research area is developing radiopharmaceutical compounds for medical imaging and targeted protein binding molecules for therapeutic applications.
Specifically, I am working on synthesising radiotracers to target the CXCR4 chemokine receptor which has been shown to be overexpressed in 23 different types of cancer.
Q: WHY DID YOU INCORPORATE THE EXPRESSION CMS INTO YOUR LABORATORY?
A: The expression CMS was purchased as we are a large research group and it is more cost and time effective to be able to carry out rapid MS analysis in situ for some sample and to use the University’s analytical service only for more complex analyses that are less time sensitive. The expression CMS fits nicely onto the bench top, performs all the functions needed for general day to day use, and is easy to use and maintain.
Q: HOW DO YOU USE THE EXPRESSION CMS?
A: We use the expression CMS to monitor chemical reactions, check for by-products and gauge the purity of our products. We have the TLC-MS interface which is extremely useful in identifying compounds straight from the TLC plate. Personally, I have used the expression CMS to examine fractions from a column to identify exactly when my product was being eluted, which would not have been possible previously. Purchasing the expression CMS has undoubtedly saved our group a great deal of time and has helped advance our research.
A: The group has comprehensive experiences for undertaking radiotracer experiments, different spectroscopic techniques, characterization of colloid-chemical properties and in vitro/in vivo studies in view of the development and characterization of novel radiotracers, including functionalized nanoparticles. The design and development of chemically, metabolically and radiolytically stable radiometal complexes on the basis of 64Cu/67Cu is of special interest. Furthermore, polynuclear metal compounds (polyoxometalates, Re clusters) for anti-tumor activity, photosensitizing, and radiation-sensitizing properties are under investigation. The characterization of binding and transport behavior of novel receptors by solvent extraction studies represents one main topic.
Q: WHAT PREVIOUS WORKFLOW CHALLENGES DID YOU EXPERIENCE?
A: The development of new bifunctional chelating agents and relevant target-seeking bio-conjugates requires novel synthetic strategies and the improvement of known pathways as well. For the successful achievement of this goal, ‘real-time’ characterization of main and side-products is of particular importance.
Q: WHY DID YOU INCORPORATE THE EXPRESSION CMS INTO YOUR LABORATORY?
A: The Advion expression compact mass spectrometer rapidly provides reliable mass data in a stand-alone modus and coupled to UPLC/HPLC systems, respectively. Sample handling and measurement are straightforward. PhD students appreciate both the ‘in-time’ information about success and failure in developing novel compounds. I recommend to all groups requiring immediate access to reliable mass data for the characterization of novel compounds.
N units are incorporated for better colorimetric responses as compared to systems having lesser number of such units. NBPBIH turns from colorless to dark yellow on exposure to F−. The detection event is well supported by UV–vis, fluorescence, 1H and 19F-NMR like spectrophotometric and cyclic voltammetric studies in DMSO because of enhanced fluorescence responses, higher Stokes shift value and for its less toxic nature compared to other solvents. Quenching of fluorescence is explained with photoinduced electron transfer mechanism (PET). The binding constant of NBPBIH with F− is around 0.84 × 105 M−1 and limit of detection of F− is found 1.42 × 10−5 M. Our concern is also to address fluorosis: an issue related to global health problem, affecting millions of common people. It is noteworthy that the existing diagnostic and treatment options are of huge expenses. As an artefact, chemoreceptor assisted simple prototype for detecting excessive fluoride in sample solution has been designed and developed which has potential and good prospect to be applied as a low cost affordable diagnostic kit for fluorosis in largely affected countries like China, India and several others.
