The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Zhuang Liu - One of the best experts on this subject based on the ideXlab platform.
-
Biomaterial-mediated internal Radioisotope Therapy
Materials Horizons, 2021Co-Authors: Pei Pei, Zhuang Liu, Teng Liu, Wenhao Shen, Kai YangAbstract:Radiation Therapy (RT), including external beam radioTherapy (EBRT) and internal Radioisotope Therapy (RIT), has been an indispensable strategy for cancer Therapy in clinical practice in recent years. Ionized atoms and free radicals emitted from the nucleus of Radioisotopes can cleave a single strand of DNA, inducing the apoptosis of cancer cells. Thus far, nuclides used for RIT could be classified into three main types containing alpha (α), beta (β), and Auger particle emitters. In order to enhance the bioavailability and reduce the physiological toxicity of Radioisotopes, various biomaterials have been utilized as multifunctional nanocarriers, including targeting molecules, macromolecular monoclonal antibodies, peptides, inorganic nanomaterials, and organic and polymeric nanomaterials. Therapeutic Radioisotopes have been labeled onto these nanocarriers via different methods (chelating, chemical doping, encapsulating, displacement) to inhibit or kill cancer cells. With the continuous development of research in this respect, more promising biomaterials as well as novel therapeutic strategies have emerged to achieve the high-performance RIT of cancer. In this review article, we summarize recent advances in biomaterial-mediated RIT of cancer and provide guidance for non-experts to understand nuclear medicine and to conduct cancer radioTherapy.
-
Nanoparticle-mediated internal Radioisotope Therapy to locally increase the tumor vasculature permeability for synergistically improved cancer therapies.
Biomaterials, 2019Co-Authors: Chao Liang, Liangzhu Feng, Xuan Yi, Yu Chao, Jun Xu, Qi Zhao, Kai Yang, Zhuang LiuAbstract:Abstract The limited tumor specific uptake of nanoparticles is one of major bottlenecks for clinical translation of nanoscale therapeutics. Herein, we propose a strategy using internal Radioisotope Therapy (RIT) delivered by liposomal nanoparticles to improve the tumor vasculature permeability, so as to increase the tumor specific uptake of the second-wave therapeutic nanoparticles for enhanced cancer therapies. Via a convenient method, a therapeutic Radioisotope iodine-131 is labeled onto albumin-encapsulated liposomes with greatly improved radiolabeling stability compared to 131 I labeled albumin. The obtained 131 I-liposome with long blood half-life could accumulate in the tumor and damage tumor blood endothelial cells to improve the tumor vascular permeability. As the result, the tumor retention of the second wave of liposomal nanoparticles could be greatly increased owing to the RIT-enhanced EPR effect. In three separated experiments, we then demonstrate that such strategy could be utilized for photothermal Therapy (PTT), hypoxia-activated chemoTherapy (HCT) and checkpoint blockade immunoTherapy, all of which could be enhanced by RIT with excellent in vivo synergistic therapeutic outcomes. Our work highlights the great promises of employing nanoparticle-mediated RIT to modulate tumor vasculature for further enhanced cancer Therapy, and may have potential value for clinical translation.
-
calcium bisphosphonate nanoparticles with chelator free radiolabeling to deplete tumor associated macrophages for enhanced cancer Radioisotope Therapy
ACS Nano, 2018Co-Authors: Longlong Tian, Yu Chao, Chao Liang, Kai Yang, Ziliang Dong, Yaxing Wang, Zhuang LiuAbstract:Tumor-associated macrophages (TAMs) are often related with poor prognosis after radioTherapy. Depleting TAMs may thus be a promising method to improve the radio-therapeutic efficacy. Herein, we report a biocompatible and biodegradable nanoplatform based on calcium bisphosphonate (CaBP-PEG) nanoparticles for chelator-free radiolabeling chemistry, effective in vivo depletion of TAMs, and imaging-guided enhanced cancer Radioisotope Therapy (RIT). It is found that CaBP-PEG nanoparticles prepared via a mineralization method with poly(ethylene glycol) (PEG) coating could be labeled with various Radioisotopes upon simple mixing, including gamma-emitting 99mTc for single-photon-emission computed tomography (SPECT) imaging, as well as beta-emitting 32P as a therapeutic Radioisotope for RIT. Upon intravenous injection, CaBP(99mTc)-PEG nanoparticles exhibit efficient tumor homing, as evidenced by SPECT imaging. Owning to the function of bisphosphonates as clinical drugs to deplete TAMs, suppressed angiogenesis, norm...
-
Combined local immunostimulatory Radioisotope Therapy and systemic immune checkpoint blockade imparts potent antitumour responses
Nature biomedical engineering, 2018Co-Authors: Yu Chao, Liangzhu Feng, Chao Liang, Kai Yang, Longlong Tian, Ziliang Dong, Zhuang LiuAbstract:Radiation Therapy for cancer can lead to off-target toxicity and can be ineffective against hypoxic solid tumours and distant metastases. Here, we show that intratumoral injection, in mouse and rabbit xenografts and in patient-derived mouse xenografts, of a sodium alginate formulation containing catalase (Cat) labelled with the therapeutic 131I Radioisotope enables long-term relief of tumour hypoxia and complete tumour elimination at low radioactivity doses. On injection, the soluble polysaccharide rapidly transforms into a hydrogel in the presence of endogenous Ca2+, fixing 131I-Cat within the tumours. We also show that local radioTherapy with a formulation that includes the immunostimulatory CpG oligonucleotide combined with systemic checkpoint-blockade Therapy using an anti-CTLA-4 antibody leads to metastasis inhibition and protection against tumour rechallenge. The local Therapy, which uses only biocompatible components, might enable new strategies for local tumour treatments that can be combined with systemic therapeutic responses, for the inhibition of tumour metastasis and the prevention of tumour recurrence in patients with advanced-stage cancer.
-
Development of a thermosensitive protein conjugated nanogel for enhanced radio-chemoTherapy of cancer.
Nanoscale, 2018Co-Authors: Debabrata Maiti, Zhuang Liu, Yu Chao, Ziliang Dong, Kai YangAbstract:Although chemo-radioTherapy has been widely applied in clinics for cancer treatment, current strategies still face many challenges including serious side-effects and drug resistance. Herein, we develop a chemically cross-linked poly-N,N'-dimethyl aminoethyl methacrylate (PDMAEMA) smart nanogel as an excellent thermosensitive nanocarrier to load both an anticancer drug, doxorubicin (DOX) and a Radioisotope, 131I-labeled albumin, for enhanced chemo-Radioisotope Therapy. Such a PDMAEMA nanogel in the solution form at room temperature can be easily injected into a tumor, in which it would be transformed into a gel at body temperature. Sustained drug release occurs in the tumor owing to the pH sensitive switching activity of the nanogel. In addition, the in situ thermogelling behavior of PDMAEMA leads to the long-term retention of 131I-labeled albumin within the tumor. In vivo chemo-radioTherapy is then conducted, achieving excellent therapeutic efficacy due to the sustained drug release and 131I retention for a long time in the cancer lesions. Our newly developed strategy of using a thermosensitive polymer for enhancing chemo-radioTherapy may be considered as a promising platform for combined cancer Therapy without inducing obvious side-effects compared to the traditional chemo or radioTherapy.
Kai Yang - One of the best experts on this subject based on the ideXlab platform.
-
Versatile labeling of multiple radionuclides onto a nanoscale metal-organic framework for tumor imaging and Radioisotope Therapy
Biomaterials science, 2021Co-Authors: Yugui Tao, Kai Yang, Pei Pei, Ge Fei, Yuanchen Sun, Kexin Shi, Teng LiuAbstract:Radionuclides for cancer theranostic have confronted problems such as limitation in real-time visualization and unsatisfactory therapeutic effect sacrificed by the nonspecific distribution. Nanoscale metal-organic frameworks (nMOFs) have been widely used in biomedical applications including cancer imaging and drug delivery. However, there have been rare reports utilizing nMOFs as a single nanoplatform to label various radionuclides for tumor imaging and Radioisotope Therapy (RIT). In this work, we developed polyethylene glycol (PEG) modified zirconium-based nMOFs (PCN-224) with favorable size, water solubility and biocompatibility. Interestingly, without the help of chelating agents, metal radionuclides (technetium-99 m/99mTc, lutetium-177/177Lu) could be efficiently labeled onto nMOFs via chelating with the porphyrin structure and iodine-125 (125I) via chemical substitution of hydrogen in the benzene ring. The radionuclide-labeled PCN-PEG nanoparticles all exhibit excellent radiolabeling stability in different solutions. In accordance with the fluorescence imaging of mice injected with PCN-PEG, SPECT/CT imaging illustrates strong tumor accumulation of 99mTc-PCN-PEG. Moreover, 177Lu-PCN-PEG significantly inhibited the growth of tumor without inducing any perceptible toxicity to the treated mice. Hence, the radionuclide-delivery nanoplatform based on nMOFs would provide more opportunities for precise tumor theranostics and expand the biomedical applications of MOF nanomaterials.
-
Biomaterial-mediated internal Radioisotope Therapy
Materials Horizons, 2021Co-Authors: Pei Pei, Zhuang Liu, Teng Liu, Wenhao Shen, Kai YangAbstract:Radiation Therapy (RT), including external beam radioTherapy (EBRT) and internal Radioisotope Therapy (RIT), has been an indispensable strategy for cancer Therapy in clinical practice in recent years. Ionized atoms and free radicals emitted from the nucleus of Radioisotopes can cleave a single strand of DNA, inducing the apoptosis of cancer cells. Thus far, nuclides used for RIT could be classified into three main types containing alpha (α), beta (β), and Auger particle emitters. In order to enhance the bioavailability and reduce the physiological toxicity of Radioisotopes, various biomaterials have been utilized as multifunctional nanocarriers, including targeting molecules, macromolecular monoclonal antibodies, peptides, inorganic nanomaterials, and organic and polymeric nanomaterials. Therapeutic Radioisotopes have been labeled onto these nanocarriers via different methods (chelating, chemical doping, encapsulating, displacement) to inhibit or kill cancer cells. With the continuous development of research in this respect, more promising biomaterials as well as novel therapeutic strategies have emerged to achieve the high-performance RIT of cancer. In this review article, we summarize recent advances in biomaterial-mediated RIT of cancer and provide guidance for non-experts to understand nuclear medicine and to conduct cancer radioTherapy.
-
The potential clinical applications of radionuclide labeled/doped gold-based nanomaterials
Radiation Medicine and Protection, 2020Co-Authors: Wenhao Shen, Pei Pei, Teng Liu, Hailin Zhou, Junxing Huang, Kai YangAbstract:Abstract Radionuclides have been widely used for multimodal imaging and Radioisotope Therapy of cancer. Various nanomaterials have been developed as excellent nanocarriers of radionuclides for the targeted delivery into tumors, in order to minimize the unnecessary side effect and enhance the therapeutic efficacy of radioTherapy. Among those nanomaterials, gold nanomaterials with tunable morphologies, easy modification, good biological safety, and radiation sensitization capability are excellent candidates for cancer theranostics. Given the superior performance of gold-based nanomaterials in biomedicine, we summary the recent advance of radionuclide labeled/doped gold-based nanomaterials for cancer theranostics. In this review article, we will discuss the methods for labelling or doping radionuclides onto gold nanomaterials, their applications for nuclear imaging and Cerenkov luminescence (CL) imaging, as well as the Radioisotope Therapy of cancer, and finally the toxicity evaluation of radionuclide labeled/doped gold-based nanomaterials. We hope that our review article would provide guidance for non-experts to design the radiolabeled nanomaterials for cancer imaging guided Therapy.
-
Nanoparticle-mediated internal Radioisotope Therapy to locally increase the tumor vasculature permeability for synergistically improved cancer therapies.
Biomaterials, 2019Co-Authors: Chao Liang, Liangzhu Feng, Xuan Yi, Yu Chao, Jun Xu, Qi Zhao, Kai Yang, Zhuang LiuAbstract:Abstract The limited tumor specific uptake of nanoparticles is one of major bottlenecks for clinical translation of nanoscale therapeutics. Herein, we propose a strategy using internal Radioisotope Therapy (RIT) delivered by liposomal nanoparticles to improve the tumor vasculature permeability, so as to increase the tumor specific uptake of the second-wave therapeutic nanoparticles for enhanced cancer therapies. Via a convenient method, a therapeutic Radioisotope iodine-131 is labeled onto albumin-encapsulated liposomes with greatly improved radiolabeling stability compared to 131 I labeled albumin. The obtained 131 I-liposome with long blood half-life could accumulate in the tumor and damage tumor blood endothelial cells to improve the tumor vascular permeability. As the result, the tumor retention of the second wave of liposomal nanoparticles could be greatly increased owing to the RIT-enhanced EPR effect. In three separated experiments, we then demonstrate that such strategy could be utilized for photothermal Therapy (PTT), hypoxia-activated chemoTherapy (HCT) and checkpoint blockade immunoTherapy, all of which could be enhanced by RIT with excellent in vivo synergistic therapeutic outcomes. Our work highlights the great promises of employing nanoparticle-mediated RIT to modulate tumor vasculature for further enhanced cancer Therapy, and may have potential value for clinical translation.
-
T1/T2-weighted magnetic resonance imaging and SPECT imaging guided combined Radioisotope Therapy and chemoTherapy using functionalized reduced graphene oxide-manganese ferrite nanocomposites
Carbon, 2019Co-Authors: Rui Qian, Debabrata Maiti, Jing Zhong, Saisai Xiong, Hailin Zhou, Ran Zhu, Jianmei Wan, Kai YangAbstract:Multimodal imaging using nanomaterials in a single platform will bring hopeful for patients, and provide exact information including the tumor location and size for doctors. Herein, we synthesize reduced graphene oxide-manganese ferrite (RGO-MnFe2O4) nanocomposites via a hydrothermal reaction, and modify nanocomposites with polyethylene glycol (PEG) to improve its biocompatibility. Interestingly, PEGylated RGO-MnFe2O4 nanocomposites possess excellent T1/T2 weighted magnetic resonance imaging (MRI) of mice bearing 4T1 tumor after intravenous (i.v.) injection. After additional Radioisotope labeling, SPECT imaging of 125I labeled RGO-MnFe2O4-PEG nanocomposites exhibit high tumor accumulation. Under the guidance of MRI/SPECT imaging, in vivo combined Radioisotope Therapy (RIT) and chemoTherapy is carried out using anticancer drug doxorubicin and 131I co-loaded RGO-MnFe2O4-PEG nanocomposites, significant inhibiting the tumor growth after intravenous injection. Moreover, 131I- RGO-MnFe2O4-PEG/DOX nanocomposites cause no obvious toxicity to treated mice after 60 days post injection. Our study further promote the biomedical applications of nano-graphene based nanocomposites.
Alexander J.b. Mcewan - One of the best experts on this subject based on the ideXlab platform.
-
131I-MIBG Therapy in a Metastatic Small Bowel Neuroendocrine Tumor Patient Undergoing Hemodialysis.
Clinical nuclear medicine, 2017Co-Authors: Behruz Rahimi, Alexander J.b. Mcewan, William Makis, T. Riauka, Don MorrishAbstract:Systemic Radioisotope Therapy with I-metaiodobenzylguanidine (I-MIBG) is an effective form of targeted Therapy for neuroendocrine tumors. One of the absolute contraindications to administering I-MIBG Therapy listed in the 2008 European Association of Nuclear Medicine guidelines is renal insufficiency requiring dialysis, although this contraindication is not evidence based. We describe a 68-year-old woman with a metastatic small bowel neuroendocrine tumor who developed renal insufficiency requiring hemodialysis. Imaging and dosimetry with I-MIBG were performed and showed that the radiation doses to the whole body and lungs were within safe limits. She was treated with 1820 MBq of I-MIBG with no short-term adverse reactions.
-
The Challenges of Treating Paraganglioma Patients with ^177Lu-DOTATATE PRRT: Catecholamine Crises, Tumor Lysis Syndrome and the Need for Modification of Treatment Protocols
Nuclear Medicine and Molecular Imaging, 2015Co-Authors: William Makis, Karey Mccann, Alexander J.b. McewanAbstract:Purpose A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted Radioisotope Therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with ^177Lu-[DOTA^0,Tyr^3]octreotate (DOTATATE) Radioisotope Therapy using established protocols. Methods and Results Three paraganglioma patients were treated with 4–5 cycles of ^177Lu-DOTATATE and were evaluated for side effects and response to Therapy. Two of the three patients developed severe adverse reactions following their first ^177Lu-DOTATATE treatment. One patient developed a catecholamine crisis and tumor lysis syndrome within hours of treatment, requiring intensive care unit (ICU) support, and another developed a catecholamine crisis 3 days after treatment, requiring hospitalization. The treatment protocols at our institution were subsequently modified by increasing the Radioisotope infusion time from 15 to 30 min, as recommended in the literature, to 2–4 h and by reducing the administered dose of ^177Lu-DOTATATE. Subsequent ^177Lu-DOTATATE treatments utilizing the modified protocols were well tolerated, and response to Therapy was achieved in all three patients, resulting in significantly improved quality of life. Conclusion ^177Lu-DOTATATE is an exciting new therapeutic option in the management of paragangliomas; however, current treatment protocols described in the literature may need to be modified by lengthening the infusion time and/or lowering the initial treatment dose to prevent or reduce the severity of adverse reactions.
-
The Challenges of Treating Paraganglioma Patients with 177 Lu-DOTATATE PRRT: Catecholamine Crises, Tumor Lysis Syndrome and the Need for Modification of Treatment Protocols
Nuclear medicine and molecular imaging, 2015Co-Authors: William Makis, Karey Mccann, Alexander J.b. McewanAbstract:Purpose A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted Radioisotope Therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with 177Lu-[DOTA0,Tyr3]octreotate (DOTATATE) Radioisotope Therapy using established protocols.
-
Incidental Acinic Cell Carcinoma of the Parotid Gland Discordant on 123I-MIBG, 111In-Octreotide, and 18F-FDG PET/CT in a Patient With Neuroendocrine Tumor of the Cecum.
Clinical nuclear medicine, 2015Co-Authors: William Makis, Karey Mccann, Alexander J.b. McewanAbstract:A 61-year-old woman diagnosed with a metastatic well-differentiated neuroendocrine tumor of the cecum was referred for Radioisotope Therapy. Although her metastatic neuroendocrine tumor was positive on both (123)I-MIBG and (111)In-octreotide, there was a left parotid mass that was octreotide avid but MIBG negative. Further investigation also showed discordance on (18)F-FDG PET/CT and excision of the mass revealed an incidental acinic cell carcinoma of the parotid gland. Somatostatin analog imaging and PRRT (peptide receptor radionuclide Therapy) may have a role in the management of acinic cell carcinoma.
-
Resolution of Malignant Ascites and Stabilization of Metastases in a Patient With Small Bowel Neuroendocrine Tumor With 177Lu-DOTATATE Following Progression After 17 131I-MIBG Treatments and ChemoTherapy.
Clinical nuclear medicine, 2015Co-Authors: William Makis, Karey Mccann, Francois A. Buteau, Alexander J.b. McewanAbstract:A 39-year-old man diagnosed with a small bowel neuroendocrine tumor metastatic to the liver, lymph nodes, and bones achieved stable disease with ¹³¹I-MIBG Therapy totalling 17 treatments over 9 years (cumulative dose of 1.9 Ci). His disease progressed after the 17th ¹³¹I-MIBG treatment, and he went on to fail chemoTherapy, developing severe ascites requiring up to 8 L of weekly paracentesis. He was referred for ¹⁷⁷Lu-[DOTA⁰,Tyr³]octreotate (DOTATATE) Therapy, and after 4 induction cycles, his ascites resolved completely, and his metastatic disease stabilized. ¹⁷⁷Lu-DOTATATE may be useful in patients with an extensive history of Radioisotope Therapy with ¹³¹I-MIBG.
Meike L. Schipper - One of the best experts on this subject based on the ideXlab platform.
-
Efficacy of ^99mTc pertechnetate and ^131I Radioisotope Therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo
European Journal of Nuclear Medicine and Molecular Imaging, 2007Co-Authors: Meike L. Schipper, Christoph G. U. Riese, Stephan Seitz, Alexander Weber, Martin Behe, Tino Schurrat, N. Schramm, Boris Keil, Heiko Alfke, Thomas M. BehrAbstract:Purpose There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of Radioisotope Therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects. Methods Biodistribution studies and in vivo Therapy experiments were performed in nude mice carrying stably NIS-expressing neuroendocrine tumor xenografts following i.v. injection of ^131I and ^99mTc pertechnetate. To show the usefulness of NIS as an imaging reporter gene, ^99mTc pertechnetate uptake was imaged in vivo using a clinical gamma camera in combination with a custom-made single pinhole collimator, followed by SPECT/small animal MRI data coregistration. Results NIS-expressing neuroendocrine tumors strongly accumulated ^131I and ^99mTc pertechnetate, as did thyroid, stomach, and salivary gland. The volume of NIS-expressing neuroendocrine tumors decreased significantly after therapeutic administration of ^131I or ^99mTc pertechnetate, whereas control tumors continued to grow. NIS-mediated uptake of ^99mTc pertechnetate could be imaged in vivo at high resolution with a clinical gamma camera equipped with a custom-made single pinhole collimator. High-resolution functional and morphologic information could be combined in a single three-dimensional data set by coregistration of SPECT and small animal MRI data. Lastly, we demonstrated a therapeutic effect of ^99mTc pertechnetate on NIS-expressing neuroendocrine tumors in cell culture and, for the first time, in vivo, thought to be due to emitted Auger and conversion electrons. Conclusions NIS-expressing neuroendocrine tumors efficiently concentrate Radioisotopes, allowing for in vivo high-resolution small animal SPECT imaging as well as rendering possible successful Radioisotope Therapy of neuroendocrine tumors.
-
efficacy of 99mtc pertechnetate and 131i Radioisotope Therapy in sodium iodide symporter nis expressing neuroendocrine tumors in vivo
European Journal of Nuclear Medicine and Molecular Imaging, 2007Co-Authors: Meike L. Schipper, Christoph G. U. Riese, Stephan Seitz, Alexander Weber, Martin Behe, Tino Schurrat, N. Schramm, Boris Keil, Heiko Alfke, Thomas M. BehrAbstract:Purpose There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of Radioisotope Therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects.
-
Evaluation of Herpes Simplex Virus 1 Thymidine Kinase-Mediated Trapping of ^131I FIAU and Prodrug Activation of Ganciclovir as a Synergistic Cancer Radio/ChemoTherapy
Molecular Imaging and Biology, 2007Co-Authors: Meike L. Schipper, Michael L. Goris, Sanjiv S. GambhirAbstract:Purpose Evaluation of selective killing of Herpes Simplex Virus 1 thymidine kinase (HSV1-tk) expressing tumors by radiolabeled ^131I-fialuridine (FIAU), and of synergy between ^131I-FIAU and Ganciclovir (GCV). Procedures HSV1-tk-expressing cell lines and parental cell lines were exposed to ^131I-FIAU alone, GCV alone, or combinations. Activity and concentration were varied widely, concurrent and sequential administrations tested, and dose rate effects were studied. Results HSV1-tk-expressing cells accumulated up to 15.7-fold more ^131I-FIAU, were growth inhibited by 2 μCi/ml, or 5 μCi/ml ^131I-FIAU, and were inhibited by two log orders lower concentrations of GCV than parental cells. However, no synergy or additive effect was observed. Dose rate variations, or sequential treatment, did not alter outcome. Conclusion Radioisotope Therapy of HSV1-tk-expressing tumor cells with ^131I-FIAU is reported for the first time. Lack of synergy between ^131I-FIAU and GCV does not warrant further investigation of combination treatment with the two agents.
-
Evaluation of herpes simplex virus 1 thymidine kinase-mediated trapping of (131)I FIAU and prodrug activation of ganciclovir as a synergistic cancer radio/chemoTherapy.
Molecular imaging and biology, 2007Co-Authors: Meike L. Schipper, Michael L. Goris, Sanjiv S. GambhirAbstract:Evaluation of selective killing of Herpes Simplex Virus 1 thymidine kinase (HSV1-tk) expressing tumors by radiolabeled 131I-fialuridine (FIAU), and of synergy between 131I-FIAU and Ganciclovir (GCV). HSV1-tk-expressing cell lines and parental cell lines were exposed to 131I-FIAU alone, GCV alone, or combinations. Activity and concentration were varied widely, concurrent and sequential administrations tested, and dose rate effects were studied. HSV1-tk-expressing cells accumulated up to 15.7-fold more 131I-FIAU, were growth inhibited by 2 μCi/ml, or 5 μCi/ml 131I-FIAU, and were inhibited by two log orders lower concentrations of GCV than parental cells. However, no synergy or additive effect was observed. Dose rate variations, or sequential treatment, did not alter outcome. Radioisotope Therapy of HSV1-tk-expressing tumor cells with 131I-FIAU is reported for the first time. Lack of synergy between 131I-FIAU and GCV does not warrant further investigation of combination treatment with the two agents.
-
Efficacy of 99mTc pertechnetate and 131I Radioisotope Therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo.
European journal of nuclear medicine and molecular imaging, 2006Co-Authors: Meike L. Schipper, Christoph G. U. Riese, Stephan Seitz, Alexander Weber, Martin Behe, Tino Schurrat, N. Schramm, Boris Keil, Heiko Alfke, Thomas M. BehrAbstract:Purpose There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of Radioisotope Therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects.
Sanjiv S. Gambhir - One of the best experts on this subject based on the ideXlab platform.
-
Evaluation of Herpes Simplex Virus 1 Thymidine Kinase-Mediated Trapping of ^131I FIAU and Prodrug Activation of Ganciclovir as a Synergistic Cancer Radio/ChemoTherapy
Molecular Imaging and Biology, 2007Co-Authors: Meike L. Schipper, Michael L. Goris, Sanjiv S. GambhirAbstract:Purpose Evaluation of selective killing of Herpes Simplex Virus 1 thymidine kinase (HSV1-tk) expressing tumors by radiolabeled ^131I-fialuridine (FIAU), and of synergy between ^131I-FIAU and Ganciclovir (GCV). Procedures HSV1-tk-expressing cell lines and parental cell lines were exposed to ^131I-FIAU alone, GCV alone, or combinations. Activity and concentration were varied widely, concurrent and sequential administrations tested, and dose rate effects were studied. Results HSV1-tk-expressing cells accumulated up to 15.7-fold more ^131I-FIAU, were growth inhibited by 2 μCi/ml, or 5 μCi/ml ^131I-FIAU, and were inhibited by two log orders lower concentrations of GCV than parental cells. However, no synergy or additive effect was observed. Dose rate variations, or sequential treatment, did not alter outcome. Conclusion Radioisotope Therapy of HSV1-tk-expressing tumor cells with ^131I-FIAU is reported for the first time. Lack of synergy between ^131I-FIAU and GCV does not warrant further investigation of combination treatment with the two agents.
-
Evaluation of herpes simplex virus 1 thymidine kinase-mediated trapping of (131)I FIAU and prodrug activation of ganciclovir as a synergistic cancer radio/chemoTherapy.
Molecular imaging and biology, 2007Co-Authors: Meike L. Schipper, Michael L. Goris, Sanjiv S. GambhirAbstract:Evaluation of selective killing of Herpes Simplex Virus 1 thymidine kinase (HSV1-tk) expressing tumors by radiolabeled 131I-fialuridine (FIAU), and of synergy between 131I-FIAU and Ganciclovir (GCV). HSV1-tk-expressing cell lines and parental cell lines were exposed to 131I-FIAU alone, GCV alone, or combinations. Activity and concentration were varied widely, concurrent and sequential administrations tested, and dose rate effects were studied. HSV1-tk-expressing cells accumulated up to 15.7-fold more 131I-FIAU, were growth inhibited by 2 μCi/ml, or 5 μCi/ml 131I-FIAU, and were inhibited by two log orders lower concentrations of GCV than parental cells. However, no synergy or additive effect was observed. Dose rate variations, or sequential treatment, did not alter outcome. Radioisotope Therapy of HSV1-tk-expressing tumor cells with 131I-FIAU is reported for the first time. Lack of synergy between 131I-FIAU and GCV does not warrant further investigation of combination treatment with the two agents.
