Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study.

Abstract:

:Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue. In this study, we demonstrate the feasibility and safety of intraoperative dual-modality imaging with the carbonic anhydrase IX (CAIX)-targeting antibody 111In-DOTA-girentuximab-IRDye800CW in clear cell renal cell carcinoma (ccRCC) patients. Methods: A phase I protein dose escalation study was performed in patients with a primary renal mass who were scheduled for surgery. 111In-DOTA-girentuximab-IRDye800CW (5, 10, 30, or 50 mg, n=3 ccRCC patients per dose level) was administered intravenously and after 4 days SPECT/CT imaging was performed. Seven days after antibody injection, surgery was performed with the use of a gamma probe and near-infrared fluorescence camera. Results: In total, fifteen patients were included (12 ccRCC, 3 CAIX-negative tumors). No study-related serious adverse events were observed. All ccRCC were visualized by SPECT/CT and localized by intraoperative gamma probe detection (mean tumor-to-normal kidney (T:N) ratio 2.5 ± 0.8), while the T:N ratio was 1.0 ± 0.1 in CAIX-negative tumors. ccRCC were hyperfluorescent at all protein doses and fluorescence imaging could be used for intraoperative tumor delineation, assessment of the surgical cavity and detection of (positive) surgical margins. The radiosignal was crucial for tumor localization in case of overlying fat tissue. Conclusion: This first in man study shows that tumor-targeted dual-modality imaging using 111In-DOTA-girentuximab-IRDye800CW is safe and can be used for intraoperative guidance of ccRCC resection.

journal_name

Theranostics

journal_title

Theranostics

authors

Hekman MC,Rijpkema M,Muselaers CH,Oosterwijk E,Hulsbergen-Van de Kaa CA,Boerman OC,Oyen WJ,Langenhuijsen JF,Mulders PF

doi

10.7150/thno.23335

subject

Has Abstract

pub_date

2018-03-08 00:00:00

pages

2161-2170

issue

8

issn

1838-7640

pii

thnov08p2161

journal_volume

8

pub_type

杂志文章
  • Sensitive detection of protein biomarkers using silver nanoparticles enhanced immunofluorescence assay.

    abstract::Detection of biomarkers is extremely important for the early diagnosis of diseases. Here, we developed an easy and highly sensitive fluorescence detection system for the determination of biomarkers by combining the rapid separation of magnetic beads and silver nanoparticles labeled antibodies. An ultrasensitive silver...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.17575

    authors: Zhao LJ,Yu RJ,Ma W,Han HX,Tian H,Qian RC,Long YT

    更新日期:2017-02-08 00:00:00

  • Sensing using rare-earth-doped upconversion nanoparticles.

    abstract::Optical sensing plays an important role in theranostics due to its capability to detect hint biochemical entities or molecular targets as well as to precisely monitor specific fundamental psychological processes. Rare-earth (RE) doped upconversion nanoparticles (UCNPs) are promising for these endeavors due to their un...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.5305

    authors: Hao S,Chen G,Yang C

    更新日期:2013-03-26 00:00:00

  • A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors.

    abstract::Cell-based immunotherapy for the treatment of hematologic malignancies, such as leukemia and lymphoma, has seen much success and played an increasingly important role in clinical studies. Nevertheless, the efficacy of immunotherapy in solid tumors still needs improvements due to the immunosuppressive properties of tum...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35900

    authors: Qian X,Shi Z,Qi H,Zhao M,Huang K,Han D,Zhou J,Liu C,Liu Y,Lu Y,Yuan X,Zhao J,Kang C

    更新日期:2019-10-14 00:00:00

  • Chronic ethanol consumption and HBV induce abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activate Tregs in HBV-Tg mice.

    abstract::Rationale: Chronic ethanol consumption as a public health problem worldwide boosts the development of chronic liver diseases in hepatitis B virus (HBV)-infected patients. Arachidonic acid metabolite prostaglandin E2 (PGE2) activates regulatory T cells (Tregs) function. Here, we aim to investigate the underlying mechan...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.46005

    authors: Liu Z,Wang J,Liu L,Yuan H,Bu Y,Feng J,Liu Y,Yang G,Zhao M,Yuan Y,Zhang H,Yun H,Zhang X

    更新日期:2020-07-23 00:00:00

  • Soluble EMMPRIN levels discriminate aortic ectasia in Marfan syndrome patients.

    abstract::Marfan syndrome (MFS) is a rare genetic disease characterized by a matrix metalloproteases (MMPs) dysregulation that leads to extracellular matrix degradation. Consequently, MFS patients are prone to develop progressive thoracic aortic enlargement and detrimental aneurysm. Since MMPs are activated by the extracellular...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.30714

    authors: Rurali E,Perrucci GL,Gaetano R,Pini A,Moschetta D,Gentilini D,Nigro P,Pompilio G

    更新日期:2019-04-12 00:00:00

  • Microporous polysaccharide multilayer coated BCP composite scaffolds with immobilised calcitriol promote osteoporotic bone regeneration both in vitro and in vivo.

    abstract::Incorporating a biomimetic coating and integrating osteoinductive biomolecules into basic bone substitutes are two common strategies to improve osteogenic capabilities in bone tissue engineering. Currently, the underlying mechanism of osteoporosis (OP)-related deficiency of osteogenesis remains unclear, and few treatm...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.29566

    authors: Tang Q,Hu Z,Jin H,Zheng G,Yu X,Wu G,Liu H,Zhu Z,Xu H,Zhang C,Shen L

    更新日期:2019-01-30 00:00:00

  • Focused ultrasound activates voltage-gated calcium channels through depolarizing TRPC1 sodium currents in kidney and skeletal muscle.

    abstract::Pulsed focused ultrasound (pFUS) technology is being developed for clinical neuro/immune modulation and regenerative medicine. Biological signal transduction of pFUS forces can require mechanosensitive or voltage-gated plasma membrane ion channels. Previous studies suggested pFUS is capable of activating either channe...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.33876

    authors: Burks SR,Lorsung RM,Nagle ME,Tu TW,Frank JA

    更新日期:2019-07-28 00:00:00

  • Nanofibrous nerve guidance conduits decorated with decellularized matrix hydrogel facilitate peripheral nerve injury repair.

    abstract::Rationale: Peripheral nerve injury (PNI) is a great challenge for regenerative medicine. Nerve autograft is the gold standard for clinical PNI repair. Due to its significant drawbacks, artificial nerve guidance conduits (NGCs) have drawn much attention as replacement therapies. We developed a combinatorial NGC consist...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.50825

    authors: Zheng C,Yang Z,Chen S,Zhang F,Rao Z,Zhao C,Quan D,Bai Y,Shen J

    更新日期:2021-01-01 00:00:00

  • The cytotoxic effects of dimethyl sulfoxide in mouse preimplantation embryos: a mechanistic study.

    abstract::Rationale: Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble substances, a vehicle for drug therapy, and a cryoprotectant for cultured cells. DMSO induced embryonic defects and its mechanism of action remains unclear. The rationale is based on the assumption that DMSO supplementation should i...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.21662

    authors: Kang MH,Das J,Gurunathan S,Park HW,Song H,Park C,Kim JH

    更新日期:2017-10-17 00:00:00

  • RUNX2 overexpression and PTEN haploinsufficiency cooperate to promote CXCR7 expression and cellular trafficking, AKT hyperactivation and prostate tumorigenesis.

    abstract::Rationale: The overall success rate of prostate cancer (PCa) diagnosis and therapy has been improved over the years. However, genomic and phenotypic heterogeneity remains a major challenge for effective detection and treatment of PCa. Efforts to better classify PCa into functional subtypes and elucidate the molecular ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.33292

    authors: Bai Y,Yang Y,Yan Y,Zhong J,Blee AM,Pan Y,Ma T,Karnes RJ,Jimenez R,Xu W,Huang H

    更新日期:2019-05-24 00:00:00

  • Biomechanically, structurally and functionally meticulously tailored polycaprolactone/silk fibroin scaffold for meniscus regeneration.

    abstract::Meniscus deficiency, the most common and refractory disease in human knee joints, often progresses to osteoarthritis (OA) due to abnormal biomechanical distribution and articular cartilage abrasion. However, due to its anisotropic spatial architecture, complex biomechanical microenvironment, and limited vascularity, m...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.44270

    authors: Li Z,Wu N,Cheng J,Sun M,Yang P,Zhao F,Zhang J,Duan X,Fu X,Zhang J,Hu X,Chen H,Ao Y

    更新日期:2020-04-06 00:00:00

  • FABP5 promotes lymph node metastasis in cervical cancer by reprogramming fatty acid metabolism.

    abstract::Patients with cervical cancer (CCa) with lymph node metastasis (LNM) have an extremely poor prognosis. Elucidation of the molecular mechanisms underlying LNM may provide clinical therapeutic strategies for CCa. Upregulation of fatty acid-binding protein 5 (FABP5) expression in CCa tumours was demonstrated to positivel...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.44868

    authors: Zhang C,Liao Y,Liu P,Du Q,Liang Y,Ooi S,Qin S,He S,Yao S,Wang W

    更新日期:2020-05-17 00:00:00

  • Nano-zymography Using Laser-Scanning Confocal Microscopy Unmasks Proteolytic Activity of Cell-Derived Microparticles.

    abstract::Cell-derived microparticles (MPs) are nano-sized vesicles released by activated cells in the extracellular milieu. They act as vectors of biological activity by carrying membrane-anchored and cytoplasmic constituents of the parental cells. Although detection and characterization of cell-derived MPs may be of high diag...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.13757

    authors: Briens A,Gauberti M,Parcq J,Montaner J,Vivien D,Martinez de Lizarrondo S

    更新日期:2016-03-02 00:00:00

  • Pancreatic stellate cells activated by mutant KRAS-mediated PAI-1 upregulation foster pancreatic cancer progression via IL-8.

    abstract::Background: The dense fibrotic stroma enveloping pancreatic tumors is a major cause of drug resistance. Pancreatic stellate cells (PSCs) in the stroma can be activated to induce intra-tumor fibrosis and worsen patient survival; however, the molecular basics for the regulation of PSC activation remains unclear. Methods...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.36830

    authors: Wang HC,Lin YL,Hsu CC,Chao YJ,Hou YC,Chiu TJ,Huang PH,Tang MJ,Chen LT,Shan YS

    更新日期:2019-09-23 00:00:00

  • Histone H3K27 methyltransferase EZH2 and demethylase JMJD3 regulate hepatic stellate cells activation and liver fibrosis.

    abstract::Rationale: As the central hallmark of liver fibrosis, transdifferentiation of hepatic stellate cells (HSCs), the predominant contributor to fibrogenic hepatic myofibroblast responsible for extracellular matrix (ECM) deposition, is characterized with transcriptional and epigenetic remodeling. We aimed to characterize t...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.46360

    authors: Jiang Y,Xiang C,Zhong F,Zhang Y,Wang L,Zhao Y,Wang J,Ding C,Jin L,He F,Wang H

    更新日期:2021-01-01 00:00:00

  • Bright Polymer Dots Tracking Stem Cell Engraftment and Migration to Injured Mouse Liver.

    abstract::Stem cell therapy holds promise for treatment of intractable diseases and injured organs. For clinical translation, it is pivotal to understand the homing, engraftment, and differentiation processes of stem cells in a living body. Here we report near-infrared (NIR) fluorescent semiconductor polymer dots (Pdots) for br...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.18614

    authors: Chen D,Li Q,Meng Z,Guo L,Tang Y,Liu Z,Yin S,Qin W,Yuan Z,Zhang X,Wu C

    更新日期:2017-04-10 00:00:00

  • Focused ultrasound as a novel strategy for noninvasive gene delivery to retinal Müller glia.

    abstract::Müller glia are specialized retinal cells with stem cell properties in fish and frogs but not in mammals. Current efforts to develop gene therapies to activate mammalian Müller glia for retinal repair will require safe and effective delivery strategies for recombinant adeno-associated viruses (AAVs), vectors of choice...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.42611

    authors: Touahri Y,Dixit R,Kofoed RH,Miloska K,Park E,Raeisossadati R,Markham-Coultes K,David LA,Rijal H,Zhao J,Lynch M,Hynynen K,Aubert I,Schuurmans C

    更新日期:2020-02-10 00:00:00

  • PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms.

    abstract::Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their clinical behavior and require therapies specially tailored according to staging, grading, origin and expression of peptide receptors. Despite extensive scientific efforts, the therapy options are still not satisfactory. The main reasons are due...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.7851

    authors: Briest F,Grabowski P

    更新日期:2014-01-29 00:00:00

  • Multiplexed non-invasive tumor imaging of glucose metabolism and receptor-ligand engagement using dark quencher FRET acceptor.

    abstract::Rationale: Following an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imag...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.45825

    authors: Rudkouskaya A,Sinsuebphon N,Ochoa M,Chen SJ,Mazurkiewicz JE,Intes X,Barroso M

    更新日期:2020-08-15 00:00:00

  • Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway.

    abstract::Rational: Ischemic injury of the skeletal muscle remains a serious clinical problem and currently there is no effective therapy. The aim of the present study is to determine whether human umbilical cord mesenchymal stem cells- derived exosomes (UMSC-Exo) could repair ischemic injury by releasing circular RNA. Methods ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.42259

    authors: Yan B,Zhang Y,Liang C,Liu B,Ding F,Wang Y,Zhu B,Zhao R,Yu XY,Li Y

    更新日期:2020-05-18 00:00:00

  • A Comprehensive Study of Vesicular and Non-Vesicular miRNAs from a Volume of Cerebrospinal Fluid Compatible with Clinical Practice.

    abstract::Cerebrospinal fluid (CSF) microRNAs (miRNAs) have emerged as potential biomarkers for minimally invasive diagnosis of central nervous system malignancies. However, despite significant advances in recent years, this field still suffers from poor data reproducibility. This is especially true in cases of infants, conside...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.31502

    authors: Prieto-Fernández E,Aransay AM,Royo F,González E,Lozano JJ,Santos-Zorrozua B,Macias-Camara N,González M,Garay RP,Benito J,Garcia-Orad A,Falcón-Pérez JM

    更新日期:2019-06-19 00:00:00

  • Loss of EGR-1 uncouples compensatory responses of pancreatic β cells.

    abstract::Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.40664

    authors: Leu SY,Kuo LH,Weng WT,Lien IC,Yang CC,Hsieh TT,Cheng YN,Chien PH,Ho LC,Chen SH,Shan YS,Chen YW,Tsai PJ,Sung JM,Tsai YS

    更新日期:2020-03-04 00:00:00

  • Ultrasmall gold nanoparticles in cancer diagnosis and therapy.

    abstract::Due to their lower systemic toxicity, faster kidney clearance and higher tumor accumulation, ultrasmall gold nanoparticles (less than 10 nm in diameter) have been proved to be promising in biomedical applications. However, their potential applications in cancer imaging and treatment have not been reviewed yet. This re...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.42471

    authors: Fan M,Han Y,Gao S,Yan H,Cao L,Li Z,Liang XJ,Zhang J

    更新日期:2020-03-31 00:00:00

  • 19q13 KRAB zinc-finger protein ZNF471 activates MAPK10/JNK3 signaling but is frequently silenced by promoter CpG methylation in esophageal cancer.

    abstract::Zinc-finger proteins (ZFPs) are the largest transcription factor family in mammals, involved in the regulation of multiple physiologic processes including cell differentiation, proliferation, apoptosis and neoplastic transformation. Approximately one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs. Methods...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.35861

    authors: Sun R,Xiang T,Tang J,Peng W,Luo J,Li L,Qiu Z,Tan Y,Ye L,Zhang M,Ren G,Tao Q

    更新日期:2020-01-12 00:00:00

  • LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription.

    abstract::Rationale: Tumor metastasis is the main cause for cancer-related death. However, the driving molecules of metastasis remain largely unknown. Here, we aim to identify long non-coding RNAs (lncRNAs) critical for human hepatocellular carcinoma (HCC) metastasis. Methods: Microarrays were used to screen a comprehensive set...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.32854

    authors: Kang CL,Qi B,Cai QQ,Fu LS,Yang Y,Tang C,Zhu P,Chen QW,Pan J,Chen MH,Wu XZ

    更新日期:2019-06-09 00:00:00

  • Potent antibacterial activity of MSI-1 derived from the magainin 2 peptide against drug-resistant bacteria.

    abstract::The structural modification of existing AMPs is an effective strategy to develop antimicrobial agents with high-efficiency, low-cost and low-toxicity antimicrobial agents. Methods: Here, we truncated 14-amino-acids at the N-terminus of MSI-78 to obtain MSI and further modified MSI to obtain four peptide analogs: MSI-1...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.39157

    authors: Ma L,Xie X,Liu H,Huang Y,Wu H,Jiang M,Xu P,Ye X,Zhou C

    更新日期:2020-01-01 00:00:00

  • Antibody affinity and valency impact brain uptake of transferrin receptor-targeted gold nanoparticles.

    abstract::Rationale: The ability to treat invalidating neurological diseases is impeded by the presence of the blood-brain barrier (BBB), which inhibits the transport of most blood-borne substances into the brain parenchyma. Targeting the transferrin receptor (TfR) on the surface of brain capillaries has been a popular strategy...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.25228

    authors: Johnsen KB,Bak M,Kempen PJ,Melander F,Burkhart A,Thomsen MS,Nielsen MS,Moos T,Andresen TL

    更新日期:2018-05-24 00:00:00

  • Exome Sequencing of Oral Squamous Cell Carcinoma Reveals Molecular Subgroups and Novel Therapeutic Opportunities.

    abstract::Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic st...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.18551

    authors: Su SC,Lin CW,Liu YF,Fan WL,Chen MK,Yu CP,Yang WE,Su CW,Chuang CY,Li WH,Chung WH,Yang SF

    更新日期:2017-02-26 00:00:00

  • Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography.

    abstract::Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-mi...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.19898

    authors: Chen H,Tong X,Lang L,Jacobson O,Yung BC,Yang X,Bai R,Kiesewetter DO,Ma Y,Wu H,Niu G,Chen X

    更新日期:2017-06-14 00:00:00

  • Longitudinal monitoring of stem cell grafts in vivo using magnetic resonance imaging with inducible maga as a genetic reporter.

    abstract:PURPOSE:The ability to longitudinally monitor cell grafts and assess their condition is critical for the clinical translation of stem cell therapy in regenerative medicine. Developing an inducible genetic magnetic resonance imaging (MRI) reporter will enable non-invasive and longitudinal monitoring of stem cell grafts ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.9436

    authors: Cho IK,Moran SP,Paudyal R,Piotrowska-Nitsche K,Cheng PH,Zhang X,Mao H,Chan AW

    更新日期:2014-07-27 00:00:00