Jamal Zweit - Academia.edu (original) (raw)
Papers by Jamal Zweit
The Journal of Nuclear Medicine, May 1, 2016
Cerium oxide nanopaticles (CONP) have unique properties in free radical scavenging. The CONP is a... more Cerium oxide nanopaticles (CONP) have unique properties in free radical scavenging. The CONP is a rare-earth metal oxide nanoparticle of the lanthanide series, which is widely used in ultraviolet absorbance, oxygen sensing and automotive catalytic convertors. This nanoparticle has both Ce3+ and Ce4+ oxidation states that could result in an auto-regenerative redox cycle between Ce3+ and Ce4+, accompanied by creation of oxygen defects on their surface and offers many active sites for free radical scavenging. CONP have demonstrated protection properties against oxidation damages in various cells and tissues. The mechanism of this, however, is poorly understood. Monitoring the interaction of CONP with biological compartments ‘in situ’ is crucial in order to understand their biochemical and physiological properties in vivo. In this study, a multifunctional nanoparticle platform was developed through an intrinsic radiolabeling strategy and extrinsic surface functionalization to combine dual imaging components such as Single Photon Emission Computed Tomography and Optical Imaging (SPECT/OI) in single nanoparticle. The cell viability, cell uptake and overall in vivo biodistribution of CONP were also manipulated through surface functionalization. The intrinsic radiolabeling strategy is demonstrated by incorporation of various radionuclides (141Ce, 111In, 65Zn) into CONP and these radiolabeled CONP (rCONP) were coated with biocompatible polymers including Dextran T10 (DT10), Poly(acrylic acid) (PAA), or functionalized DT10 (DT10-NH2, DT10-PEG and DT10-sulfobetaine). This intrinsic labeling strategy enabled quantitative in vivo SPECT imaging. Fluorescent CONP was obtained through conjugation of fluorescein isothiocynate (FITC) with DT10-NH2 rCONP and used for cell imaging. The DT10 and DT10-NH2 rCONP didn't show decreased viability up to 120 μg/ml of Cerium whilst the PAA rCONP showed decreased viability at Cerium concentrations above 40 μg/ml. Variations in blood circulation and renal/hepatic clearance of rCONP were demonstrated and were found to be dependent on surface coating and hydrodynamic size of these nanoparticles. The results of ex vivo biodistribution were reflected in SPECT imaging of 141Ce-rCONP, showing accumulation in the liver and spleen in a living mouse over a one-week period. Together, the intrinsic and extrinsic multifunctional strategy allows the determination of the biophysical properties of CONP, opening the door for their future applications for in vivo studies and biomedical imaging. Citation Format: Likun Yang, Gobalakrishnan Sundaresan, Minghao Sun, Purnima Jose, Philip R. McDonagh, Jamal Zweit. Intrinsically radiolabeled multifunctional cerium oxide nanoparticles for in vivo studies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2667. doi:10.1158/1538-7445.AM2013-2667
![Research paper thumbnail of Precursor synthesis towards the development of [124I]-labelled 2′, 2′-difluoro-2′-deoxycytidine as a potential pet radiotracer for the anticancer drug gemcitabine](https://attachments.academia-assets.com/118961920/thumbnails/1.jpg)
](Journal of Labelled Compounds and Radiopharmaceuticals, May 1, 2001
The anticancer nucleoside analogue, Gemcitabine (2', 2'difluoro-2'-deoxycytidine) 1s an active nu... more The anticancer nucleoside analogue, Gemcitabine (2', 2'difluoro-2'-deoxycytidine) 1s an active nucleoside against solid tumours. Assessment of tumour and normal tissue concentration of drug in vivo provides pharmacokinetic data that can be related to response to treatment. Towards enabling PET imaging, the synthesis of a halogenated anaIogue has been undertaken for subsequent radiolabelling with "' 1.
Springer eBooks, 2006
ABSTRACT Recent experiments have demonstrated that laser–solid interactions at intensities greate... more ABSTRACT Recent experiments have demonstrated that laser–solid interactions at intensities greater than 1019 W/cm2 can producefast electron beams of several hundred MeV [1], tens of MeV γ-rays [2, 3], up to 58MeV proton beams [4, 5], and heavier ions [6] of up to 7MeV/nucleon. One of the potential applications of the high-energy proton beams is the production of radioactive isotopes for positron emission tomography (PET). PET is a form of medical imaging requiring the production of short-lived positron emitting isotopes 11C, 13N, 15O, and 18F, by proton irradiation of natural/enriched targets using cyclotrons. PET development has been limited because of the size and shielding requirements of the nuclear installations. Recent results have shown when an intense laser beam interacts with solid targets, tens of MeV protons capable of producing PET isotopes are generated [7, 8, 9].
Cancer Immunology, Immunotherapy, Jun 25, 2018
Prostate cancer is one of the leading causes of cancer deaths, with no curative treatments once i... more Prostate cancer is one of the leading causes of cancer deaths, with no curative treatments once it spreads. Alternative therapies, including immunotherapy, have shown limited efficacy. Dendritic cells (DC) have been widely used in the treatment of various malignancies. DC capture antigens and move to the lymphoid organs where they prime naive T cells. Interaction between DC and T cells are most active in lymph nodes and suppression of DC trafficking to lymph nodes impairs the immune response. In this work, we aimed to study trafficking of DC in vivo via various routes of delivery, to optimize the effectiveness of DC-based therapy. A DC labeling system was developed using 1,1′-dioctadecyltetramethyl indotricarbocyanine Iodine for in vivo fluorescent imaging. DC harvested from C57B/6 mice were matured, labeled, and injected intravenously, subcutaneously, or intratumorally, with or without antigen loading with whole tumor lysate, into C57B/6 mice inoculated with RM-1 murine prostate tumor cells. Signal intensity was measured in vivo and ex vivo. Signal intensity at the tumor site increased over time, suggesting trafficking of DC to the tumor with all modes of injection. Subcutaneous injection showed preferential trafficking to lymph nodes and tumor. Intravenous injection showed trafficking to lungs, intestines, and spleen. Subcutaneous injection of DC pulsed with whole tumor lysate resulted in the highest increase in signal intensity at the tumor site and lymph nodes, suggesting subcutaneous injection of primed DC leads to highest preferential trafficking of DC to the immunocompetent organs.
IEEE Transactions on Nuclear Science, Aug 1, 2001
Backprojected images offer compact and accurate storage of three-dimensional (3-D) positron emiss... more Backprojected images offer compact and accurate storage of three-dimensional (3-D) positron emission tomography (PET) data and so are potentially very suited to high-resolution 3-D PET scanners. However, there are very few methods available for correcting backprojected images for the effects of scatter and random events. Scatter correction methods usually involve experimental measurement of scatter response functions or accurate simulations, and are thus limited by the accuracy of the model used. In contrast, the approach proposed here uniquely adapts a general form of a combined scatter and random response function. This method inherently does not rely upon accurate determination of the scatter and random response functions but does, however, rely upon knowledge of the attenuating object's outline. The technique is able to adapt to different imaging situations and account for detector scatter, and in particular is readily implemented in backprojection space. The method has been implemented for a small-volume HIDAC (II) PET scanner.
Digestive Diseases and Sciences, Aug 30, 2015
Applied Radiation and Isotopes, Feb 1, 2003
A method compatible with radioactive samples, capable of detecting trace volatile components in a... more A method compatible with radioactive samples, capable of detecting trace volatile components in a sample volume of ca. 1cm3 of 2-[18F]-fluoro-2-deoxy-D-glucose solution is described. The approach, based on solid phase micro-extraction gas chromatography-mass spectrometry with a carboxen/polydimethylsiloxane based fibre, was optimised with respect to extraction time (10min), extraction temperature (60°C) and phase volume ratio (1). The analysis time, including extraction,
Supplemental Figure 1: shows an example of the HPLC technique used to measure BH4:BH2 throughout ... more Supplemental Figure 1: shows an example of the HPLC technique used to measure BH4:BH2 throughout the manuscript.
Supplemental Figures Collated: All four supplemental data figures combined with description
Supplemental Figure 4: shows the response of MDA-231 xenografts to >30 days treatment with SP ... more Supplemental Figure 4: shows the response of MDA-231 xenografts to >30 days treatment with SP in terms of tumor growth measured as tumor volumes and by a Kaplan Meier analysis of animal survival.
Supplemental Figure 3: compares the effects of two NOS inhibitors on SP-increased cGMP in MCF-7 a... more Supplemental Figure 3: compares the effects of two NOS inhibitors on SP-increased cGMP in MCF-7 and MDA-231 cells.
OMICS journal of radiology, Nov 30, 2016
Multi-modality image-guided nano-theranostics T he merging of molecular imaging and nanomedicine ... more Multi-modality image-guided nano-theranostics T he merging of molecular imaging and nanomedicine is emerging as a powerful platform to comprehensively interrogate the biology of disease and working of therapies in the era of precision medicine and health. e marriage of the two disciplines stems from the natural compatibility of the biochemicals used as molecular imaging probes and nanoparticles. Nanoparticle technology is advancing at a rapid pace and is nding a "niche" in biomedical applications, including drug delivery, nano-therapeutics, multi-modality imaging and molecular diagnostics. e combination therefore of molecular imaging and nanomedicine is poised to o er a true theranostic approach in precision health. In this talk, we will highlight recent advances in multi-modality image-guided nano-theranostics, from various laboratories including ours. We will describe an "all in one" approach where therapeutic entities are imbedded within nanoparticles, the core/shell of which also serves as molecular imaging agents. e unique intrinsic approach to nano-theranostics will be exempli ed by multi-modal molecular imaging including PET/CT, SPECT/CT, MRI and photoacoustic imaging. e "all in one" concept can also accommodate multiple therapeutic strategies including photo-thermal-therapy, targeted radiotherapy, immunotherapy and chemotherapy drugs. We envision that this novel theranostic approach has promising potential for high sensitivity and quantitative imaging using clinically applicable modalities.
Journal of Nuclear Medicine, 2020
European Journal of Nuclear Medicine 1992 19 418 425, 1992
Journal of Labelled Compounds and Radiopharmaceuticals
The Journal of Nuclear Medicine, May 1, 2016
Cerium oxide nanopaticles (CONP) have unique properties in free radical scavenging. The CONP is a... more Cerium oxide nanopaticles (CONP) have unique properties in free radical scavenging. The CONP is a rare-earth metal oxide nanoparticle of the lanthanide series, which is widely used in ultraviolet absorbance, oxygen sensing and automotive catalytic convertors. This nanoparticle has both Ce3+ and Ce4+ oxidation states that could result in an auto-regenerative redox cycle between Ce3+ and Ce4+, accompanied by creation of oxygen defects on their surface and offers many active sites for free radical scavenging. CONP have demonstrated protection properties against oxidation damages in various cells and tissues. The mechanism of this, however, is poorly understood. Monitoring the interaction of CONP with biological compartments ‘in situ’ is crucial in order to understand their biochemical and physiological properties in vivo. In this study, a multifunctional nanoparticle platform was developed through an intrinsic radiolabeling strategy and extrinsic surface functionalization to combine dual imaging components such as Single Photon Emission Computed Tomography and Optical Imaging (SPECT/OI) in single nanoparticle. The cell viability, cell uptake and overall in vivo biodistribution of CONP were also manipulated through surface functionalization. The intrinsic radiolabeling strategy is demonstrated by incorporation of various radionuclides (141Ce, 111In, 65Zn) into CONP and these radiolabeled CONP (rCONP) were coated with biocompatible polymers including Dextran T10 (DT10), Poly(acrylic acid) (PAA), or functionalized DT10 (DT10-NH2, DT10-PEG and DT10-sulfobetaine). This intrinsic labeling strategy enabled quantitative in vivo SPECT imaging. Fluorescent CONP was obtained through conjugation of fluorescein isothiocynate (FITC) with DT10-NH2 rCONP and used for cell imaging. The DT10 and DT10-NH2 rCONP didn't show decreased viability up to 120 μg/ml of Cerium whilst the PAA rCONP showed decreased viability at Cerium concentrations above 40 μg/ml. Variations in blood circulation and renal/hepatic clearance of rCONP were demonstrated and were found to be dependent on surface coating and hydrodynamic size of these nanoparticles. The results of ex vivo biodistribution were reflected in SPECT imaging of 141Ce-rCONP, showing accumulation in the liver and spleen in a living mouse over a one-week period. Together, the intrinsic and extrinsic multifunctional strategy allows the determination of the biophysical properties of CONP, opening the door for their future applications for in vivo studies and biomedical imaging. Citation Format: Likun Yang, Gobalakrishnan Sundaresan, Minghao Sun, Purnima Jose, Philip R. McDonagh, Jamal Zweit. Intrinsically radiolabeled multifunctional cerium oxide nanoparticles for in vivo studies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2667. doi:10.1158/1538-7445.AM2013-2667
Journal of Labelled Compounds and Radiopharmaceuticals, May 1, 2001
The anticancer nucleoside analogue, Gemcitabine (2', 2'difluoro-2'-deoxycytidine) 1s an active nu... more The anticancer nucleoside analogue, Gemcitabine (2', 2'difluoro-2'-deoxycytidine) 1s an active nucleoside against solid tumours. Assessment of tumour and normal tissue concentration of drug in vivo provides pharmacokinetic data that can be related to response to treatment. Towards enabling PET imaging, the synthesis of a halogenated anaIogue has been undertaken for subsequent radiolabelling with "' 1.
Springer eBooks, 2006
ABSTRACT Recent experiments have demonstrated that laser–solid interactions at intensities greate... more ABSTRACT Recent experiments have demonstrated that laser–solid interactions at intensities greater than 1019 W/cm2 can producefast electron beams of several hundred MeV [1], tens of MeV γ-rays [2, 3], up to 58MeV proton beams [4, 5], and heavier ions [6] of up to 7MeV/nucleon. One of the potential applications of the high-energy proton beams is the production of radioactive isotopes for positron emission tomography (PET). PET is a form of medical imaging requiring the production of short-lived positron emitting isotopes 11C, 13N, 15O, and 18F, by proton irradiation of natural/enriched targets using cyclotrons. PET development has been limited because of the size and shielding requirements of the nuclear installations. Recent results have shown when an intense laser beam interacts with solid targets, tens of MeV protons capable of producing PET isotopes are generated [7, 8, 9].
Cancer Immunology, Immunotherapy, Jun 25, 2018
Prostate cancer is one of the leading causes of cancer deaths, with no curative treatments once i... more Prostate cancer is one of the leading causes of cancer deaths, with no curative treatments once it spreads. Alternative therapies, including immunotherapy, have shown limited efficacy. Dendritic cells (DC) have been widely used in the treatment of various malignancies. DC capture antigens and move to the lymphoid organs where they prime naive T cells. Interaction between DC and T cells are most active in lymph nodes and suppression of DC trafficking to lymph nodes impairs the immune response. In this work, we aimed to study trafficking of DC in vivo via various routes of delivery, to optimize the effectiveness of DC-based therapy. A DC labeling system was developed using 1,1′-dioctadecyltetramethyl indotricarbocyanine Iodine for in vivo fluorescent imaging. DC harvested from C57B/6 mice were matured, labeled, and injected intravenously, subcutaneously, or intratumorally, with or without antigen loading with whole tumor lysate, into C57B/6 mice inoculated with RM-1 murine prostate tumor cells. Signal intensity was measured in vivo and ex vivo. Signal intensity at the tumor site increased over time, suggesting trafficking of DC to the tumor with all modes of injection. Subcutaneous injection showed preferential trafficking to lymph nodes and tumor. Intravenous injection showed trafficking to lungs, intestines, and spleen. Subcutaneous injection of DC pulsed with whole tumor lysate resulted in the highest increase in signal intensity at the tumor site and lymph nodes, suggesting subcutaneous injection of primed DC leads to highest preferential trafficking of DC to the immunocompetent organs.
IEEE Transactions on Nuclear Science, Aug 1, 2001
Backprojected images offer compact and accurate storage of three-dimensional (3-D) positron emiss... more Backprojected images offer compact and accurate storage of three-dimensional (3-D) positron emission tomography (PET) data and so are potentially very suited to high-resolution 3-D PET scanners. However, there are very few methods available for correcting backprojected images for the effects of scatter and random events. Scatter correction methods usually involve experimental measurement of scatter response functions or accurate simulations, and are thus limited by the accuracy of the model used. In contrast, the approach proposed here uniquely adapts a general form of a combined scatter and random response function. This method inherently does not rely upon accurate determination of the scatter and random response functions but does, however, rely upon knowledge of the attenuating object's outline. The technique is able to adapt to different imaging situations and account for detector scatter, and in particular is readily implemented in backprojection space. The method has been implemented for a small-volume HIDAC (II) PET scanner.
Digestive Diseases and Sciences, Aug 30, 2015
Applied Radiation and Isotopes, Feb 1, 2003
A method compatible with radioactive samples, capable of detecting trace volatile components in a... more A method compatible with radioactive samples, capable of detecting trace volatile components in a sample volume of ca. 1cm3 of 2-[18F]-fluoro-2-deoxy-D-glucose solution is described. The approach, based on solid phase micro-extraction gas chromatography-mass spectrometry with a carboxen/polydimethylsiloxane based fibre, was optimised with respect to extraction time (10min), extraction temperature (60°C) and phase volume ratio (1). The analysis time, including extraction,
Supplemental Figure 1: shows an example of the HPLC technique used to measure BH4:BH2 throughout ... more Supplemental Figure 1: shows an example of the HPLC technique used to measure BH4:BH2 throughout the manuscript.
Supplemental Figures Collated: All four supplemental data figures combined with description
Supplemental Figure 4: shows the response of MDA-231 xenografts to >30 days treatment with SP ... more Supplemental Figure 4: shows the response of MDA-231 xenografts to >30 days treatment with SP in terms of tumor growth measured as tumor volumes and by a Kaplan Meier analysis of animal survival.
Supplemental Figure 3: compares the effects of two NOS inhibitors on SP-increased cGMP in MCF-7 a... more Supplemental Figure 3: compares the effects of two NOS inhibitors on SP-increased cGMP in MCF-7 and MDA-231 cells.
OMICS journal of radiology, Nov 30, 2016
Multi-modality image-guided nano-theranostics T he merging of molecular imaging and nanomedicine ... more Multi-modality image-guided nano-theranostics T he merging of molecular imaging and nanomedicine is emerging as a powerful platform to comprehensively interrogate the biology of disease and working of therapies in the era of precision medicine and health. e marriage of the two disciplines stems from the natural compatibility of the biochemicals used as molecular imaging probes and nanoparticles. Nanoparticle technology is advancing at a rapid pace and is nding a "niche" in biomedical applications, including drug delivery, nano-therapeutics, multi-modality imaging and molecular diagnostics. e combination therefore of molecular imaging and nanomedicine is poised to o er a true theranostic approach in precision health. In this talk, we will highlight recent advances in multi-modality image-guided nano-theranostics, from various laboratories including ours. We will describe an "all in one" approach where therapeutic entities are imbedded within nanoparticles, the core/shell of which also serves as molecular imaging agents. e unique intrinsic approach to nano-theranostics will be exempli ed by multi-modal molecular imaging including PET/CT, SPECT/CT, MRI and photoacoustic imaging. e "all in one" concept can also accommodate multiple therapeutic strategies including photo-thermal-therapy, targeted radiotherapy, immunotherapy and chemotherapy drugs. We envision that this novel theranostic approach has promising potential for high sensitivity and quantitative imaging using clinically applicable modalities.
Journal of Nuclear Medicine, 2020
European Journal of Nuclear Medicine 1992 19 418 425, 1992
Journal of Labelled Compounds and Radiopharmaceuticals