Abstract:
PURPOSE:Radioimmunotherapy uses tumor-specific antibodies to deliver therapeutic radionuclides, but hematological toxicity due to the long serum half-life of intact antibodies remains a challenge. We evaluated a smaller antibody fragment, the minibody, with faster kinetics and a potentially improved therapeutic index. PROCEDURES:The anti-prostate stem cell antigen (PSCA) minibody (A11 Mb) was radiolabeled with iodine-124 ([124I]I-A11 Mb) or conjugated with deferoxamine (DFO) and labeled with zirconium-89 ([89Zr]Zr-DFO-A11 Mb) for surrogate immunoPET to profile pharmacokinetics in a human prostate cancer xenograft model. Subsequently, minibodies labeled with two therapeutic beta emitters, directly iodinated [131I]I-A11 Mb (non-residualizing) and 177Lu chelated using DTPA ([177Lu]Lu-DTPA-A11 Mb) (residualizing), were compared for in vitro antigen-specific cytotoxicity. Full biodistribution studies (in 22Rv1-PSCA tumor bearing and hPSCA knock-in mice) were conducted for dosimetry calculations. Finally, the lead candidate [131I]I-A11 Mb was evaluated in a radioimmunotherapy experiment. Escalating single doses (3.7, 11, or 37 MBq) and saline control were administered to 22Rv1-PSCA tumor bearing mice and anti-tumor effects (tumor volume) and toxicity (body weight) were monitored. RESULTS:Minibodies radiolabeled with therapeutic beta emitters [131I]I-A11 Mb and [177Lu]Lu-DTPA-A11 Mb exhibited comparable tumor cell growth inhibition in vitro. In vivo surrogate immunoPET imaging using [89Zr]Zr-DFO-A11 Mb showed activity retention in liver and kidney up to 72 h, while [124I]I-A11 Mb cleared from liver, kidney, and blood by 48 h. Based on full biodistribution and dosimetry calculations, administering 37 MBq [131I]I-A11 Mb was predicted to deliver a favorable dose to the tumor (35 Gy), with a therapeutic index of 22 (tumor:bone marrow). For [177Lu]Lu-DTPA-A11 Mb, the kidneys would be dose-limiting, and the maximum tolerated activity (7.4 MBq) was not predicted to deliver an effective radiation dose to tumor. Radioimmunotherapy with a single dose of [131I]I-A11 Mb showed dose-dependent tumor inhibition with minimal off-target toxicity and improved median survival (19 and 24 days, P < 0.001) compared with untreated mice (12 days). CONCLUSIONS:These findings show the potential of the anti-PSCA minibody for targeted radioimmunotherapy with minimal toxicity, and the application of immunoPET and dosimetry for personalized treatment.
journal_name
Mol Imaging Bioljournal_title
Molecular imaging and biologyauthors
Tsai WK,Zettlitz KA,Dahlbom M,Reiter RE,Wu AMdoi
10.1007/s11307-020-01518-4subject
Has Abstractpub_date
2020-10-01 00:00:00pages
1380-1391issue
5eissn
1536-1632issn
1860-2002pii
10.1007/s11307-020-01518-4journal_volume
22pub_type
杂志文章abstract::Magnetic resonance imaging (MRI) requires synthesis of contrast media bearing targeting groups and numerous gadolinium chelating groups generating high relaxivity. This paper explores the results of linking the gadolinium chelates to the targeting group, a protein molecule, via various types of linkers. Polycondensate...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-010-0358-1
更新日期:2011-06-01 00:00:00
abstract:PURPOSE:Previously, some reports mentioned that magnetic resonance imaging (MRI) can predict histopathological features in primary CNS lymphoma (PCNSL). The reported data analyzed diffusion-weighted imaging findings. The aim of this study was to investigate possible associations between histopathological findings, such...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-017-1115-5
更新日期:2018-04-01 00:00:00
abstract::2'-deoxy-2'-[(18)F]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil ([(18)F]FEAU) is a promising radiolabeled nucleoside designed to monitor Herpes Simplex Virus Type 1 thymidine kinase (HSV1-tk) reporter gene expression with positron emission tomography (PET). However, the challenging radiosynthesis creates problems fo...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-007-0122-3
更新日期:2008-03-01 00:00:00
abstract:PURPOSE:The simplified reference tissue model (SRTM) is commonly applied for the quantification of brain positron emission tomography (PET) studies, particularly because it avoids arterial cannulation. SRTM requires a validated reference region which is obtained by baseline-blocking or displacement studies. Once a refe...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-020-01572-y
更新日期:2021-01-14 00:00:00
abstract:PURPOSE:Construction of antibody-based, molecular-targeted optical imaging probes requires the labeling of an antibody with a fluorophore. The most common method for doing this involves non-specifically conjugating a fluorophore to an antibody, resulting in poorly defined, heterogeneous imaging probes that often have s...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-018-1222-y
更新日期:2019-02-01 00:00:00
abstract:PURPOSE:The goal of this study was to determine the specificity of ⁶⁴Cu-CB-TE2A-c(RGDyK) (⁶⁴Cu-RGD) for osteoclast-related diseases, such as Paget's disease or rheumatoid arthritis. PROCEDURES:C57BL/6 mice were treated systemically with osteoprotegerin (OPG) for 15 days or RANKL for 11 days to suppress and stimulate o...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-011-0512-4
更新日期:2012-08-01 00:00:00
abstract:PURPOSE:2-[18F]Fluoropropionic acid (RS-[18F]FPA) has shown potential value as a short-chain fatty acid positron emission tomography (PET) tracer for the detection of liver cancer. However, RS-[18F]FPA is a mixture of 2-R-[18F]fluoropropionic acid (R-[18F]FPA) and 2-S-[18F]fluoropropionic acid (S-[18F]FPA). The aim of ...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-019-01346-1
更新日期:2019-12-01 00:00:00
abstract:PURPOSE:Magnetic resonance imaging (MRI) with targeted contrast agents provides a promising means for diagnosis and treatment monitoring after cerebrovascular injury. Our goal was to demonstrate the feasibility of this approach to detect the neuroinflammatory biomarker intercellular adhesion molecule-1 (ICAM-1) after s...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-013-0617-z
更新日期:2013-08-01 00:00:00
abstract:PURPOSE:Many neurological diseases affect small structures in the brain and, as such, reliable visual evaluation and accurate quantification are required. Recent technological developments made the clinical use of hybrid positron emission tomography/magnetic resonance (PET/MR) systems possible, providing both functiona...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-015-0824-x
更新日期:2015-10-01 00:00:00
abstract:PURPOSE:Non-invasive in vivo positron emission tomography (PET) provides high detection sensitivity in the nano- to picomolar range and in addition to other advantages, the possibility to absolutely quantify the acquired data. The present study focuses on the comparison of transmission data acquired with an X-ray compu...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-017-1074-x
更新日期:2017-12-01 00:00:00
abstract:PURPOSE:Malignant cells exhibit increased rates of aerobic glycolysis. Here, we tested whether the accumulation of fluoro-deoxyglucose-6-phosphate (FDG6P) in ovarian cancers of differential malignancy reflects inversely correlated elevations of hexokinase (HK) and glucose-6-phosphatase (G6Pase) activities. PROCEDURES:...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-018-1247-2
更新日期:2019-04-01 00:00:00
abstract:PURPOSE:The aim of this study was to determine the effect of hyperinsulinemia on myocardial and hepatic distribution and metabolism of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA). PROCEDURES:Mitochondrial retention and intracellular lipid incorporation of [18F]FTHA were compared to that of [14C]-2-bromop...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-006-0042-7
更新日期:2006-07-01 00:00:00
abstract::Atherosclerotic plaques can remain quiescent for years, but become life threatening upon rupture or disruption, initiating clot formation in the vessel lumen and causing acute myocardial infarction and ischemic stroke. Whether and how a plaque ruptures is determined by its macroscopic structure and microscopic composi...
journal_title:Molecular imaging and biology
pub_type: 杂志文章,评审
doi:10.1007/s11307-018-1264-1
更新日期:2018-12-01 00:00:00
abstract:PURPOSE:This research aimed to study the use of Cerenkov luminescence imaging (CLI) for non-Hodgkin's lymphoma (NHL) using 89Zr-rituximab positron emission tomography (PET) tracer with a humanized transgenic mouse model that expresses human CD20 and the correlation of CLI with PET. PROCEDURES:Zr-rituximab (2.6 MBq) wa...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-013-0624-0
更新日期:2013-08-01 00:00:00
abstract:PURPOSE:The mTOR kinase inhibitor AZD8055 inhibits both mTORC1 and mTORC2 leading to disruption of glucose metabolism and proliferation pathways. This study assessed the impact of single and multiple doses of AZD8055 on the uptake of the glucose metabolism marker 2-deoxy-2-[(18) F]fluoro-D-glucose ([(18) F]FDG) and the...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-013-0705-0
更新日期:2014-06-01 00:00:00
abstract:PURPOSE:Ga-68-labeled prostate-specific membrane antigen (PSMA) ligands have been used clinically for positron emission tomography (PET) imaging of prostate cancer. However, F-18-labeled compounds offer several advantages, including the potential for delayed imaging, high starting activities enabling multidose preparat...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-015-0844-6
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:Human pluripotency gene networks (PGNs), controlled in part by Oct4, are central to understanding pluripotent stem cells, but current fluorescent reporter genes (RGs) preclude noninvasive assessment of Oct4 dynamics in living subjects. PROCEDURES:To assess Oc4 activity noninvasively, we engineered a mouse embr...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-014-0744-1
更新日期:2014-12-01 00:00:00
abstract:OBJECTIVE:2-Deoxy-2-[F-18]fluoro-D-glucose positron emission tomography (FDG-PET) has an established role in restaging of various cancers, including papillary and undifferentiated thyroid carcinoma, but detection rates are variable in the published literature. We were therefore prompted to review our experience with FD...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-006-0046-3
更新日期:2006-09-01 00:00:00
abstract:PURPOSE:The purpose of the study is to synthesize and characterize near-infrared (NIR) fluorescence imaging probes targeted to gelatinases. PROCEDURES:A phage display-selected cyclic peptide containing the His-Try-Gly-Phe (HWGF) motif was used as the lead compound. Structure-activity relationship analysis was used to ...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-009-0219-y
更新日期:2009-11-01 00:00:00
abstract:PURPOSE:The purpose of the study was to examine the feasibility of an antibody-carrying targeted-bubble preparation using clinically available phosphatidylserine (PS)-containing perfluorobutane-filled microbubbles for molecular ultrasound imaging. PROCEDURES:Firstly, we examined whether PS on the surface of perfluorob...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-010-0344-7
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:Macrophage accumulation characterizes the development of atherosclerotic plaques, and the presence of certain macrophage subsets might be an indicator of plaque phenotype and (in)stability. The macrophage mannose receptor (MMR) is expressed on alternatively activated macrophages and found at sites of intraplaqu...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-017-1117-3
更新日期:2018-04-01 00:00:00
abstract:PURPOSE:We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of ...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-017-1125-3
更新日期:2018-04-01 00:00:00
abstract:PURPOSE:To determine the prevalence of viable myocardium in patients with ischemic cardiomyopathy and, to evaluate the value of three-dimensional (3-D) fusion imaging of myocardial scintigraphic and angiographic data to assign coronary artery lesions to the corresponding viable and nonviable myocardial territory. PROC...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1016/j.mibio.2004.02.002
更新日期:2004-05-01 00:00:00
abstract:PURPOSE:In this study, the contrasting properties of human serum albumin nanoparticles (HSA-NPs) loaded with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and coated with transferrin in MRI in mice are evaluated. PROCEDURES:HSA-NPs were conjugated with Gd-DTPA (Gd-HSA-NPs) and coupled with transferrin (Gd-H...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-012-0579-6
更新日期:2013-04-01 00:00:00
abstract:PURPOSE:The A1AR antagonist 8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([(18)F]CPFPX) has recently been shown to be a suitable radiotracer for quantitative in vivo imaging of the A1 adenosine receptor (A1AR) in rats. The present study evaluates the reproducibility of non-invasive longitudinal A1AR studies with [...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-014-0729-0
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:CXCR4 is overexpressed on tumor cells from many types of human cancers. A high level of CXCR4 expression often correlates with poor prognosis, chemotherapy resistance, and metastasis. The development of CXCR4-specific radiotracers for positron emission tomography (PET) imaging will allow in vivo evaluation of r...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-013-0640-0
更新日期:2013-12-01 00:00:00
abstract::Positron emission tomography (PET) with epidermal growth factor receptor (EGFR) kinase-specific radiolabeled tracers could provide the means for noninvasive and repetitive imaging of heterogeneity of EGFR expression and signaling activity in tumors in individual patients before and during therapy with EGFR signaling i...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-006-0049-0
更新日期:2006-09-01 00:00:00
abstract:PURPOSE:The purpose of this study was to assess the value of the spatial heterogeneity of somatostatin receptor (SSR) volume, quantified as asphericity (ASP), and to predict response to peptide receptor radionuclide therapy (PRRT) in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). P...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-016-1018-x
更新日期:2017-06-01 00:00:00
abstract:PURPOSE:This study aims to determine a lumped constant (LC) value that can be applied to the 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography (FDG-PET) study to yield a physiological value of cerebral metabolic rate of glucose (CMR(glc)) in normal brain. PROCEDURES:We developed a more robust method for dete...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1016/s1536-1632(02)00122-1
更新日期:2003-01-01 00:00:00
abstract:PURPOSE:Recent studies have shown rapid accumulation of nanobodies (NBs) in tumors and fast clearance of the unbound fraction, making NBs exceptional tracers for cancer imaging. In this study, we investigate the combination of in vitro imaging of tumor spheroids, in vivo dual-isotope single-photon emission computed tom...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-019-01320-x
更新日期:2019-12-01 00:00:00