ORCID Profile
0000-0003-3084-2084
Current Organisation
Peter MacCallum Cancer Centre
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Publisher: Wiley
Date: 20-03-2023
Abstract: Efficient methods for labeling aryl trifluoromethyl groups to provide novel radiotracers for use in biomedical research with positron emission tomography (PET) are keenly sought. We report a broad‐scope method for labeling trifluoromethylarenes with either carbon‐11 ( t 1/2 =20.4 min) or fluorine‐18 ( t 1/2 =109.8 min) from readily accessible aryl(mesityl)iodonium salts. In this method, the aryl(mesityl)iodonium salt is treated rapidly with no‐carrier‐added [ 11 C]CuCF 3 or [ 18 F]CuCF 3 . The mesityl group acts as a spectator allowing radiolabeled trifluoromethylarenes to be obtained with very high chemoselectivity. Radiochemical yields from aryl(mesityl)iodonium salts bearing either electron‐donating or electron‐withdrawing groups at meta ‐ or para ‐ position are good to excellent (67–96 %). Ortho ‐substituted and otherwise sterically hindered trifluoromethylarenes still give good yields (15–34 %). Substituted heteroaryl(mesityl)iodonium salts are also viable substrates. The broad scope of this method was further exemplified by labeling a previously inaccessible target, [ 11 C] p ‐trifluoromethylphenyl boronic acid, as a potentially useful labeling synthon. In addition, fluoxetine, leflunomide, and 3‐trifluoromethyl‐4‐aminopyridine, as ex les of small drug‐like molecules and candidate PET radioligands, were successfully labeled in high yields (69–81 %).
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0MD00140F
Abstract: A comparative study of PNP- and TFP-activated esters of radiolabelled prosthetic groups demonstrates the superiority of PNP esters in terms of stability and yields for use in one-step radiolabelling of small molecules and peptides.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2021
DOI: 10.1007/S10989-021-10310-Z
Abstract: Many cancers of neuroendocrine origin overexpress cholecystokinin-2 receptors (CCK-2R) including medullary thyroid cancer, small cell lung cancer and other lung carcinoids. Fluorine-18 labelled peptides targeting CCK-2R enable direct visualization and quantification of this receptor in vivo using positron emission tomography imaging. CP04 1 and MG11 2 are two previously described truncated peptides derived from the native CCK-2R hormone ligand, gastrin. The N -terminus of the MG11 2 octopeptide was chemically modified with various fluorine containing aromatic (4-fluorobenzoate), heterocyclic (6-fluoronicotinate) and aliphatic (2-fluoropropionate) moieties. To assess the impact these modifications had on CCK-2R binding, ligand-binding assays were conducted using A431 cells overexpressing human CCK-2R. MG11 2 modified by 4-fluorobenzoate (FB-MG11 3 ) demonstrated the highest binding affinity (0.20 nM) followed by MG11 2 modified by 6-fluoronicotinate (FNic-MG11 4 0.74 nM) and 2-fluoropropionate (FP-MG11 5 1.80 nM), respectively. Whilst indirect labelling of MG11 2 using fluorine-18 labelled activated esters of fluorobenzoate and 6-fluoronicotinate was unsuccessful, direct fluorine-18 labelling at the N -terminus modified with 6-nitronicotinate afforded a 47.6% radiochemical yield of [ 18 F]FNic-MG11. Unfortunately, [ 18 F]FNic-MG11 4 was chemically unstable, decomposing slowly through defluorination, thereby impeding any further work with this radiotracer.
Publisher: MDPI AG
Date: 13-09-2009
DOI: 10.3390/MOLECULES27185931
Abstract: (1) Background: [18F]Flumazenil 1 ([18F]FMZ) is an established positron emission tomography (PET) radiotracer for the imaging of the gamma-aminobutyric acid (GABA) receptor subtype, GABAA in the brain. The production of [18F]FMZ 1 for its clinical use has proven to be challenging, requiring harsh radiochemical conditions, while affording low radiochemical yields. Fully characterized, new methods for the improved production of [18F]FMZ 1 are needed. (2) Methods: We investigate the use of late-stage copper-mediated radiofluorination of aryl stannanes to improve the production of [18F]FMZ 1 that is suitable for clinical use. Mass spectrometry was used to identify the chemical by-products that were produced under the reaction conditions. (3) Results: The radiosynthesis of [18F]FMZ 1 was fully automated using the iPhase FlexLab radiochemistry module, affording a 22.2 ± 2.7% (n = 5) decay-corrected yield after 80 min. [18F]FMZ 1 was obtained with a high radiochemical purity ( %) and molar activity (247.9 ± 25.9 GBq/µmol). (4) Conclusions: The copper-mediated radiofluorination of the stannyl precursor is an effective strategy for the production of clinically suitable [18F]FMZ 1.
Publisher: Wiley
Date: 09-09-2020
Publisher: American Chemical Society (ACS)
Date: 07-04-2021
Publisher: Wiley
Date: 05-09-2019
Abstract: Molecules containing lysine-ureido-glutamate functional groups bind to the active site of prostate specific membrane antigen, which is overexpressed in prostate cancer. To prepare copper radiopharmaceuticals for the diagnosis and therapy of prostate cancer, macrobicyclic sarcophagine ligands tethered to either one or two lysine-ureido-glutamate functional groups through an appropriate linker have been prepared. Sarcophagine ligands can be readily radiolabeled with positron-emitting copper-64 at room temperature. The bivalent agent, in which two targeting groups are tethered to a single copper complex, dramatically outperforms the monomeric agent with respect to tumor uptake and retention. The high tumor uptake, low background, and prolonged tumor retention, even at 24 hours post injection, suggest the bivalent agent is a promising diagnostic for prostate cancer and could be used for prospective dosimetry for therapy with a copper-67 variant.
Publisher: American Chemical Society (ACS)
Date: 31-03-2021
DOI: 10.1021/ACS.BIOCONJCHEM.1C00109
Abstract: Radiolabeled derivatives of Tyr
Publisher: Wiley
Date: 05-09-2019
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-05-2020
DOI: 10.1126/SCITRANSLMED.AAU2939
Abstract: Two radioligands, [ 18 F]LSN3316612 and [ 11 C]LSN3316612, image and quantify brain O -linked-β- N -acetyl-glucosamine hydrolase in vivo.
Publisher: CSIRO Publishing
Date: 08-11-2021
DOI: 10.1071/CH21118
Abstract: Theranostics are drugs suitable for use in both diagnostic and therapeutic applications, and have played an important role in the advancement of modern nuclear medicine. This review explains key elements that are common to successful theranostics and highlights significant developments in the field, including our own. Specific focus is given to peptides and those features that make them most suitable for theranostic application, as well as some key radioisotopes owing to their favourable properties and high clinical utility. This report provides an overview of the techniques at the researcher’s disposal, how they have been applied to current clinically significant targets, and how they might be used and improved upon for future targets.
Publisher: Springer Science and Business Media LLC
Date: 2022
Publisher: American Chemical Society (ACS)
Date: 26-07-2023
No related grants have been discovered for Mohammad Haskali.