Garry Kiefer - Academia.edu (original) (raw)

Papers by Garry Kiefer

Nuclear medicine and …, Jan 1, 2007

Three 1, 4, 7, 10-tetraazacyclododecane-N, N′, Nʺ, Nʺ′-tetraacetic acid (DOTA) analogues were eva... more Three 1, 4, 7, 10-tetraazacyclododecane-N, N′, Nʺ, Nʺ′-tetraacetic acid (DOTA) analogues were evaluated for relative in vivo stability when radiolabeled with 111In, 90Y and 177Lu and conjugated to the monoclonal antibody B72. 3. The DOTA analogues ...

Journal of magnetism …, Jan 1, 2005

The relaxivity and transmetallation of two lipophilic paramagnetic chelates incorporated onto per... more The relaxivity and transmetallation of two lipophilic paramagnetic chelates incorporated onto perfluorocarbon nanoparticles, i.e., gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid phosphatidylethanolamine (Gd-MeO-DOTA-PE) and gadolinium-methoxy-tetraazacyclododecane-tetraacetic acid triglycine phosphatidylethanolamine (Gd-MeO-DOTA-triglycine-PE (Gd-MeO-DOTA-triglycine-PE)), were compared to a prototypic gadoliniumdiethylene-triamine-pentaacetic acid bis-oleate (Gd-DTPA-BOA) paramagnetic formulation. Nanoparticles with MeO-DOTA-based chelates demonstrated higher relaxivity (40% higher for Gd-MeO-DOTA-PE and 55% higher for Gd-MeO-DOTA-triglycine-PE) and less transmetallation than the original Gd-DTPA-BOA-based agent. r 2005 Published by Elsevier B.V.

Journal of the …, Jan 1, 2008

Linear polymers of PARACEST agents were prepared by using classical free radical chain polymeriza... more Linear polymers of PARACEST agents were prepared by using classical free radical chain polymerization conditions. The Eu 3+ -polymers exhibited similar intermediate-to-slow water exchange and CEST characteristics as the Eu 3+ -monomers. This provided an avenue to lower the detection limit of these imaging agents substantially and makes them potentially useful as MRI sensors for molecular imaging.

Inorganic Chemistry, Jan 1, 1997

ABSTRACT

The Journal of Organic …, Jan 1, 1986

... Synthesis of Halogenated Terpyridines and Incorporation of the Terpyridine Nucleus into a Pol... more ... Synthesis of Halogenated Terpyridines and Incorporation of the Terpyridine Nucleus into a Polyethereal Macrocycle' George R. Newkome,* David C. Hager, and Garry E. Kiefer ... Chem. SOC. 1979, 101, 4472. (3) Newkome, G. R.; Kohli, DK; Fronczek, FR J. Chem. SOC., Chem. ...

European journal of …, Jan 1, 2010

PurposeImmuno-PET is an emerging imaging tool for the selection of high potential antibodies (mAb... more PurposeImmuno-PET is an emerging imaging tool for the selection of high potential antibodies (mAbs) for imaging and therapy. The positron emitter zirconium-89 (89Zr) has attractive characteristics for immuno-PET with intact mAbs. Previously, we have described a multi-step procedure for stable coupling of 89Zr to mAbs via the bifunctional chelate (BFC) tetrafluorophenol-N-succinyldesferal (TFP-N-sucDf). To enable widespread use of 89Zr-immuno-PET, we now introduce the novel BFC p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) and compare its performance in 89Zr-immuno-PET with the reference BFC TFP-N-sucDf.MethodsThree mAbs were premodified with Df-Bz-NCS and labeled with 89Zr at different pHs to assess the reaction kinetics and robustness of the radiolabeling. Stability of both 89Zr-Df-Bz-NCS- and 89Zr-N-sucDf-conjugates was evaluated in different buffers and human serum. Comparative biodistribution and PET studies in tumor-bearing mice were undertaken.ResultsThe selected conjugation conditions resulted in a chelate:mAb substitution ratio of about 1.5:1. Under optimal radiolabeling conditions (pH between 6.8–7.2), the radiochemical yield was >85% after 60 min incubation at room temperature, resulting in radioimmunoconjugates with preserved integrity and immunoreactivity. The new radioimmunoconjugate was very stable in serum for up to 7 days at 37°C, with <5% 89Zr release, and was equally stable compared to the reference conjugate when stored in the appropriate buffer at 4°C. In biodistribution and imaging experiments, the novel and the reference radioimmunoconjugates showed high and similar accumulation in tumors in nude mice.ConclusionsThe novel Df-Bz-NCS BFC allows efficient and easy preparation of optimally performing 89Zr-labeled mAbs, facilitating further exploration of 89Zr-immuno-PET as an imaging tool.

Journal of the …, Jan 1, 1982

... George R. Newkome,* Frank R. Fronczek, V. K. Gupta,2a Wallace E. Puckett, Daniel C. Pantaleo,... more ... George R. Newkome,* Frank R. Fronczek, V. K. Gupta,2a Wallace E. Puckett, Daniel C. Pantaleo,2b and Garry E. Kiefer ... (1) Chemistry of Heterocyclic Compounds. Part 78. Previous related paper in this series: Newkome, G. R.; Kohli, DK; Fronczek, FR J. Am. Chem. SOC. ...

Bioconjugate …, Jan 1, 2004

A derivative of 1,10-phenanthroline that binds to UO(2)(2+) with nanomolar affinity was found to ... more A derivative of 1,10-phenanthroline that binds to UO(2)(2+) with nanomolar affinity was found to be a very effective immunogen for the generation of antibodies directed toward chelated complexes of hexavalent uranium. This study describes the synthesis of 5-isothiocyanato-1,10-phenanthroline-2,9-dicarboxylic acid and its use in the generation and functional characterization of a group of monoclonal antibodies that recognize the most soluble and toxic form of uranium, the hexavalent uranyl ion (UO(2)(2+)). Three different monoclonal antibodies (8A11, 10A3, and 12F6) that recognize the 1:1 complex between UO(2)(2+) and 2,9-dicarboxy-1,10-phenanthroline (DCP) were produced by the injection of BALB/c mice with DCP-UO(2)(2+) covalently coupled to a carrier protein. Equilibrium dissociation constants for the binding of DCP-UO(2)(2+) to antibodies 8A11, 10A3, and 12F6 were 5.5, 2.4, and 0.9 nM, respectively. All three antibodies bound the metal-free DCP with roughly 1000-fold lower affinity. The second-order rate constants for the bimolecular association of each antibody with soluble DCP-UO(2)(2+) were in the range of 1 to 2 x 10(7) M(-1) s(-1). Binding studies conducted with structurally related chelators and 21 metal ions demonstrated that each of these three antibodies was highly specific for the soluble DCP-UO(2)(2+) complex. Detailed equilibrium binding studies conducted with three other derivatives of DCP, either complexed with UO(2)(2+) or metal-free, suggested that the antigen binding sites on the three antibodies have significant functional and structural similarities. Biomolecules that bind specifically to uranium will be at the heart of any new biotechnology developed to monitor and control uranium contamination. The three antibodies described herein possess sufficient affinity and specificity to support the development of immunoassays for hexavalent uranium in environmental and clinical samples.

Investigative …, Jan 1, 2009

BackgroundThe use of antiangiogenic therapy in conjunction with traditional chemotherapy is becom... more BackgroundThe use of antiangiogenic therapy in conjunction with traditional chemotherapy is becoming increasingly in cancer management, but the optimal benefit of these targeted pharmaceuticals has been limited to a subset of the population treated. Improved imaging probes that permit sensitive detection and high-resolution characterization of tumor angiogenesis could improve patient risk-benefit stratification.ObjectivesThe overarching objective of these experiments was to develop a dual modality αvβ3-targeted nanoparticle molecular imaging agent that affords sensitive nuclear detection in conjunction with high-resolution MR characterization of tumor angiogenesis.Materials and MethodsIn part 1, New Zealand white rabbits (n = 21) bearing 14d Vx2 tumor received either αvβ3-targeted 99mTc nanoparticles at doses of 11, 22, or 44 MBq/kg, nontargeted 99mTc nanoparticles at 22 MBq/kg, or αvβ3-targeted 99mTc nanoparticles (22 MBq/kg) competitively inhibited with unlabeled αvβ3-nanoparticles. All animals were imaged dynamically over 2 hours with a planar camera using a pinhole collimator. In part 2, the effectiveness of αvβ3-targeted 99mTc nanoparticles in the Vx2 rabbit model was demonstrated using clinical SPECT-CT imaging techniques. Next, MR functionality was incorporated into αvβ3-targeted 99mTc nanoparticles by inclusion of lipophilic gadolinium chelates into the outer phospholipid layer, and the concept of high sensitivity – high-resolution detection and characterization of tumor angiogenesis was shown using sequential SPECT-CT and MR molecular imaging with 3D neovascular mapping.Resultsαvβ3-Targeted 99mTc nanoparticles at 22 MBq/kg produced the highest tumor-to-muscle contrast ratio (8.56 ± 0.13, TMR) versus the 11MBq/kg (7.32 ± 0.12) and 44 MBq/kg (6.55 ± 0.07) doses, (P < 0.05). TMR of nontargeted particles at 22.2 MBq/kg (5.48 ± 0.09) was less (P < 0.05) than the equivalent dosage of αvβ3-targeted 99mTc nanoparticles. Competitively inhibition of 99mTc αvβ3-integrin-targeted nanoparticles at 22.2 MBq/kg reduced (P < 0.05) TMR (5.31 ± 0.06) to the nontargeted control contrast level. Multislice CT imaging could not distinguish the presence of Vx2 tumor implanted in the popliteal fossa from lymph nodes in the same fossa or in the contralateral leg. However, the use of 99mTc αvβ3-nanoparticles with SPECT-CT produced a clear neovasculature signal from the tumor that was absent in the nonimplanted hind leg. Using αvβ3-targeted 99mTc-gadolinium nanoparticles, the sensitive detection of the Vx2 tumor was extended to allow MR molecular imaging and 3D mapping of angiogenesis in the small tumor, revealing an asymmetrically distributed, patchy neovasculature along the periphery of the cancer.ConclusionDual modality molecular imaging with αvβ3-targeted 99mTc-gadolinium nanoparticles can afford highly sensitive and specific localization of tumor angiogenesis, which can be further characterized with high-resolution MR neovascular mapping, which may predict responsiveness to antiangiogenic therapy.

Inorganic …, Jan 1, 1992

Optimized Synthesis, Structure, and Solution Dynamics of 1,4,7,1O-Tetraazacyclododecane-1,4,7,10-... more Optimized Synthesis, Structure, and Solution Dynamics of 1,4,7,1O-Tetraazacyclododecane-1,4,7,10-tetraus( methylenephosphonic acid) (HsMITP) ... Istvhn M r , + Duane C. Hmcir,* Won-he Kim,* Carry E. Kiefer,f and A. Dean Sherry&#x27;** Department of Inorganic and ...

Inorganic …, Jan 1, 1985

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Inorganic Chemistry, Jan 1, 1995

Department of Chemistry, University of Texas at Dallas, Richardson, Texas 75083-0688, and Designe... more Department of Chemistry, University of Texas at Dallas, Richardson, Texas 75083-0688, and Designed Chemicals R &amp; D, Dow Chemical Co., Freeport, Texas 77541 ... Tetraazamacrocycles containing the pyridine moiety as part of the cyclic backbone and acetate pendant arms ...

Magnetic resonance …, Jan 1, 2006

A lipid-encapsulated perfluorocarbon nanoparticle molecular imaging contrast agent utilizing a PA... more A lipid-encapsulated perfluorocarbon nanoparticle molecular imaging contrast agent utilizing a PARAmagnetic Chemical Exchange Saturation Transfer (PARACEST) chelate is presented. PARACEST agents are ideally suited for molecular imaging applications because the contrast can be switched on and off at will simply by adjusting pulse sequence parameters. This obviates the need for pre-and post-injection images in order to define contrast agent binding. Spectroscopy (4.7 T) of PARACEST nanoparticles revealed a bound water peak at 52 ppm, in agreement with results from the water-soluble chelate. Imaging of control nanoparticles showed no appreciable contrast, while PARACEST nanoparticles produced >10% signal enhancement. PARACEST nanoparticles were targeted to clots via anti-fibrin antibodies and produced a contrast-to-noise ratio of 10 at the clot surface.

Journal of the …, Jan 1, 2004

Two gadolinium(III) chelates, GdNP-DO3A (1-methlyene-(p-NitroPhenol)-1,4,7,10-tetraazacycloDOdeca... more Two gadolinium(III) chelates, GdNP-DO3A (1-methlyene-(p-NitroPhenol)-1,4,7,10-tetraazacycloDOdecane-4,7,10-triAcetate) and GdNP-DO3AM (1-methlyene(p-NitroPhenol)-1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide), containing a single nitrophenolic pendant arm plus either three acetate or three amide pendant arms were synthesized and characterized. The properties of the gadolinium, terbium, and dysprosium complexes of these ligands were examined as a function of pH. The extent and mechanism of the changes in water relaxivity with pH of each gadolinium complex was found to differ substantially for the two complexes. The water relaxivity of Gd(NP-DO3A) increases from 4.1 mM −1 s −1 at pH 9 to 7.0 mM −1 s −1 at pH 5 as a result of acid-catalyzed dissociation of the nitrophenol from the lanthanide. The nitrophenol group in Gd(NP-DO3AM) does not dissociate from the metal center even at pH 5; therefore, the very modest increase in relaxivity in this complex must be ascribed to an increase in prototropic exchange rate of the bound water and/or phenolic protons.

Analytical …, Jan 1, 1999

In-vivo and in-vitro investigations indicate that a newly developed polyazamacrocyclic chelate of... more In-vivo and in-vitro investigations indicate that a newly developed polyazamacrocyclic chelate of Tb(III) has superior properties for use as an abnormal tissue marker. In addition to tissue selectivity, this molecule is unique because of its low toxicity, attractive fluorescent properties, rapid pharmokinetics, and relatively high water solubility. The complex Tb-3,6,9-tris(methylene phosphonic acid n-butyl ester)-3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13 -triene (Tb-PCTMB) has also been shown to exhibit strongly shifted emission (delta lambda--280 nm), moving the detection frequency away from autofluorescence backgrounds, and good quantum efficiencies (phi = 0.51), providing high brightness. Fluorescence imaging was used to quantify Tb-PCTMB at the picomolar level in tissues and to show the significant difference in affinity for the chelate by adenocarcinoma cells HT-29 versus normal epithelial cells (IEC-6). Topical application, or lavage introduction, under endoscopy was used to instill a millimolar aqueous solution of Tb-PCTMB into a dimethylhydrizene-treated Sprague Dawley rat large intestine containing a suspect growth. Subsequent in vitro fluorescence detection and standard histological evaluation confirmed enhanced uptake by adenocarcinoma tissue. Semiquantitative signal interrogation was employed to show the potential for using Tb-PCTMB as a contrast enhancement marker for disease detection.

… journal of cancer, Jan 1, 2007

Earlier tumor detection can improve 5-year survival of patients, particularly among those present... more Earlier tumor detection can improve 5-year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. a m b 3 -Targeted 111 In nanoparticles (NP) were developed and studied for detection of tumor angiogenesis. Studies were conducted in New Zealand white rabbits implanted 12 days earlier with Vx-2 tumor. a m b 3 -Targeted 111 In/NP bearing 10 111 In/NP vs. 1 111 In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand-targeting specificity. a m b 3 -Integrin-targeted NP with 10 111 In/NP provided better (p < 0.05) tumor-to-muscle ratio contrast (6.3 6 0.2) than 1 111 In/NP (5.1 6 0.1) or nontargeted particles with 10 111 In/NP (3.7 6 0.1) over the initial 2-hr postinjection. At 18 hr, mean tumor activity in rabbits receiving a m b 3 -integrin-targeted NP was 4-fold higher than the nontargeted control. Specificity of the NP for the tumor neovasculature was supported by in vivo competition studies and by fluorescence microscopy of a m b 3 -targeted fluorescent-labeled NP. Biodistribution studies revealed that the primary clearance organ in rabbits as a %ID/g tissue was the spleen. Circulatory half-life (t 1/2b ) was estimated to be 5 hr using a 2-compartment model. a m b 3 -Targeted 111 In perfluorocarbon NP may provide a clinically useful tool for sensitively detecting angiogenesis in nascent tumors, particularly in combination with secondary highresolution imaging modalities, such as MRI. ' 2007 Wiley-Liss, Inc.

Inorganic …, Jan 1, 1995

... (7) Kim, WD; Hmcir, DC; Kiefer, GE; Sherry, A. D ... In a typical complex formation experimen... more ... (7) Kim, WD; Hmcir, DC; Kiefer, GE; Sherry, A. D ... In a typical complex formation experiment, 1 .OO mL of 0.1 M LnC13 solution was mixed with 1.05 mL of 0.1 M ligand, and the sample was neutralized with KOH and finally diluted to 5.00 mL to make a 20 mM stock solution of the ...

Journal of Magnetic Resonance ( …, Jan 1, 1992

Complexes between the trivalent lanthanide ions and the macrocyclic chelate 1,4,7,10-tetraazacycl... more Complexes between the trivalent lanthanide ions and the macrocyclic chelate 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetra(methylene phosphonate) (DOTP).

Chemical …, Jan 1, 1986

Page 1. Chem. Rev. 1988, 86, 451-489 45 1 Cyclometalation of the Platinum Metals with Nitrogen an... more Page 1. Chem. Rev. 1988, 86, 451-489 45 1 Cyclometalation of the Platinum Metals with Nitrogen and Alkyl, Alkenyl, and Benzyl Carbon Donors GEORGE R. NEWKOME,*+ WALLACE E. PUCKETT, VINOD K. GUPTA, and GARRY E. KIEFER ...

Journal of the …, Jan 1, 1989

Recently, t h e series of halogen-bridged M"-X-MIV mixedvalence compounds (M = Pt, Pd, and N i ) ... more Recently, t h e series of halogen-bridged M"-X-MIV mixedvalence compounds (M = Pt, Pd, and N i ) h a s attracted much interest from solid-state physicists and chemists as one-dimensional materials having s t r o n g electron-lattice interaction.2 Their (1) Present address, National Institute for Research in Ionorganic Materials, Tsukuba, Ibaraki 305, Japan.