@article {SOUTHCOTT2022111936,
	title = {Trastuzumab-conjugated oxine-based ligand for [89Zr]Zr4+ immunoPET},
	journal = {J. Inorg. Biochem.},
	volume = {235},
	year = {2022},
	month = {07/2022},
	pages = {111936. Invited for Special Issue: Celebrating 50 Years of the Journal of Inorganic Biochemistry},
	abstract = {<p>A new, bifunctional chelating ligand for immuno-Positron Emission Tomography (PET) was designed, synthesized, and conjugated to Trastuzumab for a proof-of-concept study with 89Zr. H4neunox was synthesized from the tris(2-aminoethyl)amine backbone, decorated with 8-hydroxyquinoline moieties, and utilizes a primary amine for functionalization. A maleimide moiety extends the chelator to create H4neunox-mal for antibody conjugation via maleimide-thiol click chemistry. Preliminary 89Zr radiolabeling of H4neunox indicated quantitative radiolabeling at 1 \&times; 10\&minus;5 M, but improved inertness towards human serum (96\% intact at 7 d) and Fe3+ (92\% intact at 24 h) compared to the previously synthesized H5decaox. The chelator was successfully conjugated to the monoclonal antibody, Trastuzumab, and used in preliminary radiolabeling reactions (37 \&deg;C, 2 h) with 89Zr. Radiochemical assessments of the new H4neunox-Trastuzumab conjugate include 89Zr radiolabeling, spin filter purification, cell-binding immunoreactivity, and in vivo PET imaging and biodistribution in SKOV-3 tumour bearing nude mice, performed in comparison with the desferrioxamine B analog, DFO-Trastuzumab. The [89Zr]Zr(neunox-Trastuzumab) showed lowered inertness towards serum (76\% intact at 24 h) as well as demetallation in vivo through bone uptake (21\% ID/g) in PET imaging and biodistribution studies when compared to [89Zr]Zr(DFO-Trastuzumab). Although the combination of the chelator and antibody had detrimental effects on their intended purposes, nonetheless, the primary amine platform of H4neunox developed here provides an oxine-based bifunctional ligand for further derivatizations with other targeting vectors.</p>},
	keywords = {89Zr, BIODISTRIBUTION, immunopet, Neunox, Oxine-ligand conjugate, Trastuzamab},
	issn = {0162-0134},
	doi = {https://doi.org/10.1016/j.jinorgbio.2022.111936},
	url = {https://www.sciencedirect.com/science/article/pii/S0162013422002252},
	author = {Lily Southcott and Luke Wharton and Julie Rousseau and Helen Merkens and Hua Yang and Fran{\c c}ois B{\'e}nard and Chris Orvig}
}
@article {RADCHENKO2016280,
	title = {Labeling and preliminary in vivo assessment of niobium-labeled radioactive species: A proof-of-concept study},
	journal = {Nuclear Medicine and Biology},
	volume = {43},
	number = {5},
	year = {2016},
	pages = {280 - 287},
	abstract = {The application of radionuclide-labeled biomolecules such as monoclonal antibodies or antibody fragments for imaging purposes is called immunoscintigraphy. More specifically, when the nuclides used are positron emitters, such as zirconium-89, the technique is referred to as immuno-PET. Currently, there is an urgent need for radionuclides with a half-life which correlates well with the biological kinetics of the biomolecules under question and which can be attached to the proteins by robust labeling chemistry. 90Nb is a promising candidate for in vivo immuno-PET, due its half-life of 14.6h and low β+ energy of Emean=0.35MeV per decay. 95Nb on the other hand, is a convenient alternative for longer-term ex vivo biodistribution studies, due to its longer half-life of (t{\textonehalf}=35days) and its convenient, lower-cost production (reactor-based production). In this proof-of-principle work, the monoclonal antibody bevacizumab (Avastin{\textregistered}) was labeled with 95/90Nb and in vitro and in vivo stability was evaluated in normal Swiss mice and in tumor-bearing SCID mice. Initial ex vivo experiments with 95Nb-bevacizumab showed adequate tumor uptake, however at the same time high uptake in the liver, spleen and kidneys was observed. In order to investigate whether this behavior is due to instability of ⁎Nb-bevacizumab or to the creation of other ⁎Nb species in vivo, we performed biodistribution studies of 95Nb-oxalate, 95Nb-chloride and 95Nb-Df. These potential metabolite species did not show any specific uptake, apart from bone accumulation for 95Nb-oxalate and 95Nb-chloride, which, interestingly, may serve as an {\textquotedblleft}indicator{\textquotedblright} for the release of 90Nb from labeled biomolecules. Concerning the initial uptake of 95Nb-bevacizumab in non-tumor tissue, biodistribution of a higher specific activity radiolabeled antibody sample did show only negligible uptake in the liver, spleen, kidneys or bones. In-vivo imaging of a tumor-bearing SCID mouse after injection with 90Nb-bevacizumab was acquired on an experimental small-animal PET camera, and indeed showed localization of the radiotracer in the tumor area. It is the first time that such results are described in the literature, and indicates promise of application of 90Nb-labeled antibodies for the purposes of immuno-PET.},
	keywords = {Bevacizumab, BIODISTRIBUTION, Labeling, Nb, PET imaging, VEGFR},
	issn = {0969-8051},
	doi = {https://doi.org/10.1016/j.nucmedbio.2016.02.003},
	url = {http://www.sciencedirect.com/science/article/pii/S0969805115300627},
	author = {Valery Radchenko and Penelope Bouziotis and Theodoros Tsotakos and Mari Paravatou-Petsotas and Ana de la Fuente and George Loudos and Adrian L. Harris and Stavros Xanthopoulos and Dmitry Filosofov and Harald Hauser and Michael Eisenhut and Bernard Ponsard and Frank Roesch}
}
@article {2637,
	title = {Vanadium treatment of type 2 diabetes: A view to the future},
	journal = {Journal of Inorganic Biochemistry},
	volume = {103},
	number = {4},
	year = {2009},
	note = {ISI Document Delivery No.: 429EUTimes Cited: 20Cited Reference Count: 41Thompson, Katherine H. Lichter, Jay LeBel, Carl Scaife, Michael C. McNeill, John H. Orvig, Chris6th International Vanadium SymposiumJUL 17-19, 2008Lisbon, PORTUGALSp. Iss. SI},
	month = {Apr},
	pages = {554-558},
	type = {Proceedings Paper},
	abstract = {3-Hydroxy-2-methyl-4-pryone and 2-ethyl 3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable a ligands for vanadyl tons, fit potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pie-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL2) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a ran-e of doses horn 10 mg, to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects, all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020). 20 mg, daily for 28 clays, per os, in seven type 2 diabetic Subjects, was associated with reductions in fasting blood and glucose and \%HbA1c; improved responses to oral glucose tolerance testing, versus, the observed worsening of diabetic symptoms in the two placebo controls. (C) 2009 Elsevier Inc. All rights reserved.},
	keywords = {BIODISTRIBUTION, bis(ethylmaltolato)oxovanadium(IV), BIS(MALTOLATO)OXOVANADIUM(IV), CHEMISTRY, Diabetes mellitus, IN-VIVO, INSULIN SENSITIVITY, MALTOL, METAL-COMPLEXES, RATS, SERUM, SKELETAL-MUSCLE, SULFATE, VANADIUM},
	isbn = {0162-0134},
	url = {<Go to ISI>://000264904400011},
	author = {Thompson, K. H. and Lichter, J. and Lebel, C. and Scaife, M. C. and McNeill, J. H. and Orvig, Chris}
}
@article {2287,
	title = {Toward [F-18]-labeled aryltrifluoroborate radiotracers: In vivo positron emission tomography imaging of stable aryltrifluoroborate clearance in mice},
	journal = {Journal of the American Chemical Society},
	volume = {130},
	number = {36},
	year = {2008},
	note = {ISI Document Delivery No.: 344TPTimes Cited: 15Cited Reference Count: 35Ting, Richard Harwig, Curtis auf dem Keller, Ulrich McCormick, Siobhan Austin, Pamela Overall, Christopher M. Adam, Michael J. Ruth, Thomas J. Perrin, David M.},
	month = {Sep},
	pages = {12045-12055},
	type = {Article},
	abstract = {The use of a boronic ester as a captor of aqueous [F-18]-fluoride has been previously suggested as a means of labeling biomolecules in one step for positron emission tomography (PET) imaging. For this approach to be seriously considered, the [F-18]-labeled trifluoroborate should be humorally stable such that it neither leaches free [F-18]-fluoride to the bone nor accumulates therein. Herein, we have synthesized a biotinylated boronic ester that is converted to the corresponding trifluoroborate salt in the presence of aqueous [F-18]-fluoride. In keeping with its in vitro aqueous kinetic stability at pH 7.5, the trifluoroborate appears to clear in vivo quite rapidly to the bladder as the stable trifluoroborate salt with no detectable leaching of free [F-18]-fluoride to the bone. When this labeled biotin is preincubated with avidin, the pharmacokinetic clearance of the resulting complex is visibly altered. This work validates initial claims that boronic esters are potentially useful as readily labeled precursors to [F-18]-PET reagents.},
	keywords = {apoptosis, BIODISTRIBUTION, CANCER, DESIGN, F-18, MICROPET, NO-CARRIER, PEPTIDES, PET, STABILITY},
	isbn = {0002-7863},
	url = {<Go to ISI>://000258950500044},
	author = {Ting, R. and Harwig, C. and auf dem Keller, U. and McCormick, S. and Austin, P. and Overall, C. M. and Adam,Michael J. and Ruth, T. J. and Perrin,David M.}
}
@article {2287,
	title = {Toward [F-18]-labeled aryltrifluoroborate radiotracers: In vivo positron emission tomography imaging of stable aryltrifluoroborate clearance in mice},
	journal = {Journal of the American Chemical Society},
	volume = {130},
	number = {36},
	year = {2008},
	note = {ISI Document Delivery No.: 344TPTimes Cited: 15Cited Reference Count: 35Ting, Richard Harwig, Curtis auf dem Keller, Ulrich McCormick, Siobhan Austin, Pamela Overall, Christopher M. Adam, Michael J. Ruth, Thomas J. Perrin, David M.},
	month = {Sep},
	pages = {12045-12055},
	type = {Article},
	abstract = {The use of a boronic ester as a captor of aqueous [F-18]-fluoride has been previously suggested as a means of labeling biomolecules in one step for positron emission tomography (PET) imaging. For this approach to be seriously considered, the [F-18]-labeled trifluoroborate should be humorally stable such that it neither leaches free [F-18]-fluoride to the bone nor accumulates therein. Herein, we have synthesized a biotinylated boronic ester that is converted to the corresponding trifluoroborate salt in the presence of aqueous [F-18]-fluoride. In keeping with its in vitro aqueous kinetic stability at pH 7.5, the trifluoroborate appears to clear in vivo quite rapidly to the bladder as the stable trifluoroborate salt with no detectable leaching of free [F-18]-fluoride to the bone. When this labeled biotin is preincubated with avidin, the pharmacokinetic clearance of the resulting complex is visibly altered. This work validates initial claims that boronic esters are potentially useful as readily labeled precursors to [F-18]-PET reagents.},
	keywords = {apoptosis, BIODISTRIBUTION, CANCER, DESIGN, F-18, MICROPET, NO-CARRIER, PEPTIDES, PET, STABILITY},
	isbn = {0002-7863},
	url = {<Go to ISI>://000258950500044},
	author = {Ting, R. and Harwig, C. and auf dem Keller, U. and McCormick, S. and Austin, P. and Overall, C. M. and Adam,Michael J. and Ruth, T. J. and Perrin,David M.}
}
@article {435,
	title = {Evaluation of tetraphenyl-2,3-dihydroxychlorins as potential photosensitizers},
	journal = {Journal of Porphyrins and Phthalocyanines},
	volume = {6},
	number = {2},
	year = {2002},
	note = {ISI Document Delivery No.: 595XYTimes Cited: 15Cited Reference Count: 33},
	pages = {146-155},
	type = {Article},
	abstract = {A series of beta,beta-dihydroxychlorins derived from meso-tetraphenylporphyrins (TPPs) have been synthesized. Their in vitro cytotoxicity has been measured and compared to BPDMA (verteporfin). Under the assay conditions BPDMA had an LD50 (lethal dose to kill 50\% of cells) value of 0.007 muM (5 ng/mL). The LD50 values for the TPP derivatives varied from 1.7 x 10(-2) to 9.9 muM depending upon the substituents and their position on the phenyl groups. One example of the dihydroxychlorin prepared from unsubstituted 5,15-diphenylporphyrin was examined and this exhibited an LD50 of 2.4 x 10(-3) muM! Copyright (C) 2002 Society of Porphyrins \& Phthalocyanines.},
	keywords = {AGGREGATION, BACTERIOCHLORINS, beta, beta-dihydroxychlorins, BIODISTRIBUTION, chlorins, cytotoxicity, DERIVATIVES, photodynamic, PHOTODYNAMIC THERAPY, PHOTOPHYSICAL PROPERTIES, PHOTOSENSITIZERS, porphyrins, PROTEIN-BINDING, SENSITIZERS, therapy, TUMOR PHOTOSENSITIZERS},
	isbn = {1088-4246},
	url = {<Go to ISI>://000178134600008},
	author = {Macalpine, J. K. and Boch, R. and Dolphin, D.}
}
@article {7357,
	title = {POLYDENTATE LIGAND CHEMISTRY OF GROUP 13 METALS - EFFECTS OF THE SIZE AND DONOR SELECTIVITY OF METAL-IONS ON THE STRUCTURES AND PROPERTIES OF ALUMINUM, GALLIUM, AND INDIUM COMPLEXES WITH POTENTIALLY HEPTADENTATE (N4O3) AMINE PHENOL LIGANDS},
	journal = {Inorganic Chemistry},
	volume = {31},
	number = {26},
	year = {1992},
	note = {ISI Document Delivery No.: KE754Times Cited: 0Cited Reference Count: 37},
	month = {Dec},
	pages = {5400-5407},
	type = {Article},
	abstract = {{The aluminum, gallium and indium complexes of potentially heptadentate (N4O3) tripodal amine phenol ligands (H3L1 = tris(2{\textquoteright}-hydroxybenzylaminoethyl)amine},
	keywords = {BIODISTRIBUTION, MULTIDENTATE LIGANDS, MYOCARDIAL IMAGING AGENT, TMPHPG},
	isbn = {0020-1669},
	url = {<Go to ISI>://A1992KE75400015},
	author = {Shuang, L. and Rettig, S. J. and Orvig, Chris}
}
@article {7397,
	title = {POTENTIAL GA-67 RADIOPHARMACEUTICALS FOR MYOCARDIAL IMAGING - TRIS(1-ARYL-3-HYDROXY-2-METHYL-4-PYRIDINONATO)GALLIUM(III) COMPLEXES},
	journal = {Nuclear Medicine and Biology},
	volume = {19},
	number = {3},
	year = {1992},
	note = {ISI Document Delivery No.: HL213Times Cited: 36Cited Reference Count: 33},
	month = {Apr},
	pages = {327-335},
	type = {Article},
	abstract = {A series of highly lipophilic complexes of 1-aryl-3-hydroxy-2-methyl-4-pyridinones with gallium(III)-67 has been evaluated in vitro and in vivo as potential radiopharmaceuticals. The pyridinones have different substituents at the para -position of the phenyl ring: R = H, CH3, OCH3 and NO2. Biodistribution studies of Ga-67 complexes have been carried out in rabbits, mice, rats and a dog. High heart uptake of the radionuclide has been shown in rabbits and the dog. The different biodistribution patterns in mice and rats indicate that there is a species difference in the biodistribution of these complexes. Rabbits and the dog show rapid heart uptake and blood clearance. The speciation of the Ga3+ ion in vivo is simulated in vitro with a simple blood plasma model based on the available thermodynamic data.},
	keywords = {3-HYDROXY-4-PYRIDINONES, aluminum, BIODISTRIBUTION, CHELATING LIGAND, CHEMISTRY, gallium, INDIUM COMPLEXES, MULTIDENTATE LIGANDS, N, N{\textquoteright}-DIACETIC ACID, N{\textquoteright}-DIPYRIDOXYLETHYLENEDIAMINE-N, TRIVALENT METAL-IONS},
	isbn = {0883-2897},
	url = {<Go to ISI>://A1992HL21300012},
	author = {Zhang, Z. H. and Lyster, D. M. and Webb, G. A. and Orvig, Chris}
}
