Publications by authors named "Joseph A Ioppolo"

9 Publications

  • Page 1 of 1

Direct in vivo comparison of [F]PSMA-1007 with [Ga]Ga-PSMA-11 and [F]AlF-PSMA-11 in mice bearing PSMA-expressing xenografts.

Appl Radiat Isot 2020 Jul 2;161:109164. Epub 2020 Apr 2.

Medical Technology and Physics Department, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, WA, 6009, Australia; Department of Physics, University of Western Australia, Crawley, WA, 6009, Australia.

The aim of this preclinical study was to directly compare [F]PSMA-1007 with both [Ga]Ga-PSMA-11 and [F]AlF-PSMA-11 in mice bearing PSMA-positive tumor xenografts. Uptake was assessed by PET/CT at 1, 2 and 4 h post-injection, and by ex vivo measurement after 4 h. [F]PSMA-1007 demonstrated the highest tumor uptake of the three tracers. The high uptake in bone for mice injected with [F]AlF-PSMA-11 suggested rapid in vivo decomposition. This was confirmed by an in vitro plasma stability study.
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http://dx.doi.org/10.1016/j.apradiso.2020.109164DOI Listing
July 2020

Ga-labeled deferoxamine derivatives for imaging bacterial infection: Preparation and screening of functionalized siderophore complexes.

Nucl Med Biol 2017 Sep 1;52:32-41. Epub 2017 Jun 1.

Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada; Department of Biochemistry & Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada. Electronic address:

Introduction: Deferoxamine (DFO) is a siderophore that bacteria use to scavenge iron and could serve as a targeting vector to image bacterial infection where current techniques have critical limitations. [Ga]-DFO, which is a mimetic of the corresponding iron complex, is taken up by bacteria in culture, however in vivo it clears too rapidly to allow for imaging of infection. In response, we developed several new DFO derivatives to identify those that accumulate in bacteria, and at sites of infection, and that could potentially have improved pharmacokinetics.

Methods: A library of DFO derivatives was synthesized by functionalizing the terminal amine group of DFO using three different carbamate-forming reactions. Uptake of [Ga]-DFO and the Ga-labeled derivatives by bacteria and the biodistribution of lead compounds were studied.

Results: Ga-labeled DFO derivatives were prepared and isolated in >90% radiochemical yield and >95% radiochemical purity. The derivatives had significant but slower uptake rates in Staphylococcus aureus than [Ga]-DFO (6% to 60% of the control rate), with no uptake for the most lipophilic derivatives. Biodistribution studies in mice with a S. aureus infection in one thigh revealed that the ethyl carbamate derivative had an excellent infected-to-non-infected ratio (11:1), but high non-specific localization in the gall bladder, liver and small intestine.

Conclusions: The work reported shows that it is possible to functionalize DFO-type siderophores and retain active uptake of the Ga-labeled complexes by bacteria. Novel Ga-labeled DFO derivatives were specifically taken up by S. aureus and selected derivatives demonstrated in vivo localization at sites of infection. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Ga-labeled DFO derivatives were actively transported by bacteria using the iron-siderophore pathway, suggesting that it is possible to develop siderophore-based radiopharmaceuticals for imaging bacterial infection.
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http://dx.doi.org/10.1016/j.nucmedbio.2017.05.010DOI Listing
September 2017

New functionalized mercaptoundecahydrododecaborate derivatives for potential application in boron neutron capture therapy: synthesis, characterization and dynamic visualization in cells.

Eur J Med Chem 2015 Mar 20;93:574-83. Epub 2015 Feb 20.

Department of Chemistry, Faculty of Science, University of Tanta, 31527 Tanta, Egypt.

A series of mercaptoundecahydrododecaborate (B12H11SH(2-), BSH) bearing mono- and dicarboxyalkyl derivatives was prepared, characterized, and their reactivity towards amidation and esterification in DMF was evaluated. Symmetrical alkylation of BSH was achieved by treatment with primary haloalkyl carboxylic acids in aqueous acetonitrile to produce S,S-bis(carboxyalkyl)sulfonium-undecahydro-closo-dodecaborate tetramethylammonium salts. Unsymmetrically substituted sulfonium salts were obtained through a similar treatment of cyanoethylthioether-undecahydro-closo-dodecaborate tetramethylammonium salt with haloalkyl carboxylic acid. Selective removal of the remaining cyanoethyl group upon treatment with tetramethylammonium hydroxide yielded S-carboxyalkyl-thioether-undecahydro-closo-dodecaborate ditetramethylammonium salts. N,N'-dicyclohexylcarbodiimide (DCC) activated amidation of S,S-bis(carboxyalkyl)sulfonium-undecahydro-closo-dodecaborate or S-carboxyalkyl-thioether-undecahydro-closo-dodecaborate tetramethylammonium salts with propargylamine provided the opportunity to install terminal acetylene groups for further conjugation. These compounds acted as powerful building blocks for the synthesis of a broad range of 1,4-disubstituted 1,2,3-triazole products in high yields, utilizing the Cu(I)-mediated click cycloaddition reaction. The synthesis of BSH-lipid with a two-tailed moiety was also achieved, by esterification of S,S-bis(carboxyethyl)sulfoniumundecahydro-closo-dodecaborate(1-) tetramethylammonium salt with 1,2-O-distearoyl-sn-3-glycerol, which may prove useful in the liposomal boron delivery system. The bio-compatibility of the azide-alkyne click reaction was then utilized by performing this reaction in cell culture. The distribution of BSH in HeLa cells could be visualized by treating the cells first with a BSH-alkyne compound and then with Alexa Fluor 488(®) azide dye. The BSH-dye conjugate, which did not wash out, revealed the distribution of boron in the HeLa cells. Cytotoxicity assays of these BSH derivatives revealed that the synthesized BSH-conjugated triazoles possessed low cytotoxicity in HeLa cancer cells. Of these compounds, BSH conjugated triazole 15 induced a significant increase in the level of boron accumulation in HeLa cells.
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http://dx.doi.org/10.1016/j.ejmech.2015.02.033DOI Listing
March 2015

The first indoleamine-2,3-dioxygenase-1 (IDO1) inhibitors containing carborane.

Dalton Trans 2014 Jul;43(28):10719-24

School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

Indoleamine-2,3-dioxygenase-1 (IDO1) is a critical immunoregulatory enzyme responsible for the metabolism of tryptophan during inflammation and disease. Based upon a pyranonaphthoquinone framework, the first examples of indoleamine-2,3-dioxygenase-1 (IDO1) inhibitors containing a carborane cage are reported. The novel closo-1,2-carboranyl-N-pyranonaphthoquinone derivatives display low μM binding affinity for the human recombinant enzyme, with IC50 values ranging from 0.78 to 1.77 μM.
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http://dx.doi.org/10.1039/c4dt00444bDOI Listing
July 2014

High yielding synthesis of carboranes under mild reaction conditions using a homogeneous silver(I) catalyst: direct evidence of a bimetallic intermediate.

Angew Chem Int Ed Engl 2014 May 2;53(20):5156-60. Epub 2014 Apr 2.

Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St W., Hamilton, Ont., L8S 4M1 Canada; Department of Chemistry, Faculty of Science, Tanta University, 31527 Tanta (Egypt).

Methods used to prepare functionalized carboranes generally require heating to high temperatures, and thus limits the range of derivatives which can be prepared directly from alkynes. We show here that by using a homogeneous silver(I) catalyst it is now possible to prepare carboranes in good to excellent yield at temperatures below 40 °C, including at room temperature. The process is general and provides an important new synthetic strategy for the preparation of functionalized boron clusters.
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http://dx.doi.org/10.1002/anie.201311012DOI Listing
May 2014

High mitochondrial accumulation of new gadolinium(III) agents within tumour cells.

Chem Commun (Camb) 2014 Mar 19;50(18):2252-4. Epub 2013 Dec 19.

School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

The first bifunctional Gd(III) complexes covalently bound to arylphosphonium cations and the first tumour-cell selective mitochondrial agents designed for potential application in binary cancer therapies are reported. The highest in vitro cellular uptake for any Gd complex reported to date is described, with levels exceeding 10(10) Gd atoms per tumour cell.
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http://dx.doi.org/10.1039/c3cc46903dDOI Listing
March 2014

Remarkable cage deboronation and rearrangement of a closo-1,12-dicarbadodecaborane to form a neutral nido-7,9-dicarbaundecaborane.

Chem Commun (Camb) 2013 Apr;49(32):3312-4

School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

Deboronation and cage rearrangement of the closo-1,12-carborane salt [1,12-(PPh2Me)2-1,12-C2B10H10]I2 occurs in refluxing methanol to give the zwitterionic nido-7,9-carborane 7,9-(PPh2Me)2-7,9-C2B9H9. Notably, deboronation and cage substitution of the isomeric closo-1,7-carborane salt [1,7-(PPh2Me)2-1,7-C2B10H10]I2 takes place in methanol to afford the salt [10-OMe-7,9-(PPh2Me)2-7,9-C2B9H9]I.
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http://dx.doi.org/10.1039/c3cc41173gDOI Listing
April 2013

[1,2-Bis(diphenyl-phosphino)-1,2-dicarba-closo-dodeca-borane-κP,P'][7,8-bis-(di-phenyl-phosphino)-7,8-dicarba-nido-undeca-borato-κP,P']gold(I)-dichloro-methane-water (2/1/1).

Acta Crystallogr Sect E Struct Rep Online 2009 Apr 30;65(Pt 5):m603-4. Epub 2009 Apr 30.

The title compound, [Au(C(26)H(30)B(10)P(2))(C(26)H(30)B(9)P(2))]·0.5CH(2)Cl(2)·0.5H(2)O, contains two independent complex mol-ecules in the asymmetric unit. The gold(I) centres display a distorted tetra-hedral geometry. The complex is stablized through weak intra-molecular π-π stacking (Cg⋯Cg = 4.17 Å) and edge-to-face inter-actions (H⋯Cg = 3.21 Å). Adjacent mol-ecules inter-act through C-H⋯π (H⋯Cg = 2.88 Å) and B-H⋯π (H⋯Cg = 3.15 Å) contacts, forming a three-dimensional network, with solvent mol-ecules occupying the cavities. One of the phenyl groups was disordered over two sites with occupancy factors of 0.65 and 0.35.
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http://dx.doi.org/10.1107/S1600536809014937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977637PMC
April 2009

Dicarba-closo-dodecaborane(12) derivatives of phosphonium salts: easy formation of nido-carborane phosphonium zwitterions.

Dalton Trans 2007 May 14(20):1982-5. Epub 2007 Mar 14.

School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

The first examples of arylphosphonium salts containing a dicarba-closo-dodecaborane(12) (closo-carborane) are reported; in contrast to the 1,12-carborane derivative, the 1,2- and 1,7-isomers undergo a facile deboronation reaction in polar solvents to afford the corresponding nido-carborane phosphonium zwitterions.
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http://dx.doi.org/10.1039/b700689fDOI Listing
May 2007