Abstract:
PURPOSE:Prostate-specific membrane antigen (PSMA) continues to be the hallmark biomarker for prostate cancer as it is expressed on nearly all prostatic tumors. In addition, increased PSMA expression correlates with castration resistance and progression to the metastatic stage of the disease. Recently, we combined both an albumin-binding motif and an irreversible PSMA inhibitor to develop the novel PSMA-targeted radiotherapeutic agent, CTT1403. This molecule was novel in the field of PSMA-targeted agents as its key motifs resulted in extended blood circulation time and tumor uptake, rapid and extensive internalization into PSMA+ cells, and promising therapeutic efficacy. The objective of this study was to perform IND-enabling translational studies on CTT1403 in rodent models. PROCEDURES:A dose optimization study was performed in PC3-PIP (PSMA+) tumor-bearing mice. Treatment groups were randomly selected to receive one to three 14-MBq injections of CTT1403. Control groups included (1) saline, (2) non-radioactive [175Lu]CTT1403, or (3) two injections of 14 MBq CTT1751, a Lu-177-labeled non-targeted albumin-binding moiety. Tumor growth was monitored up to 120 days. Small-animal single photon emission tomography/X-ray computed tomography imaging was performed with CTT1403 and CTT1751 in PC3-PIP tumor-bearing mice to visualize infiltration of the Lu-177-labeled agent into the tumor. In preparation for a first-in-human study, human absorbed doses were estimated based on rat biodistribution out to 5 weeks to determine a safe CTT1403 therapy dose in humans. RESULTS:Two to 3 injections of 14 MBq CTT1403 yielded significant tumor growth inhibition and increased survival compared with all control groups and mice receiving 1 injection of 14 MBq CTT1403. Five of 12 mice receiving 2 or 3 injections of CTT1403 survived to the 120-day post-treatment study endpoint. Dosimetry identified the kidneys as the dose-limiting organ, with an equivalent dose of 5.18 mSv/MBq, resulting in a planned maximum dose of 4.4 GBq for phase 1 clinical trials. CONCLUSIONS:The preclinical efficacy and dosimetry of CTT1403 suggest that this agent has significant potential to be safe and effective in humans.
journal_name
Mol Imaging Bioljournal_title
Molecular imaging and biologyauthors
Ling X,Latoche JD,Choy CJ,Kurland BF,Laymon CM,Wu Y,Salamacha N,Shen D,Geruntho JJ,Rigatti LH,Windish HP,Langton-Webster B,Berkman CE,Anderson CJdoi
10.1007/s11307-019-01404-8subject
Has Abstractpub_date
2020-04-01 00:00:00pages
274-284issue
2eissn
1536-1632issn
1860-2002pii
10.1007/s11307-019-01404-8journal_volume
22pub_type
杂志文章abstract:PURPOSE:Although current therapies for many inflammatory/autoimmune diseases are effective, a significant number of patients still exhibit only partial or negligible responses to therapeutic intervention. Since prolonged use of an inadequate therapy can result in both progressive tissue damage and unnecessary expense, ...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-015-0876-y
更新日期:2016-04-01 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:We aimed to elucidate trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18)F]FACBC) uptake mechanisms in inflammatory and tumor cells, in comparison with those of L-[methyl-(11)C]methionine ([(11)C]Met) and 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG). PROCEDURES:Using carbon-14-labeled tracers...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-013-0693-0
更新日期:2014-06-01 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::This article reviews positron emission tomography (PET) studies of labeled enantiomers of different PET-tracers from the early 1980s. Comparative studies on stereoselective behavior of the transport of tracers across the blood-brain barrier (BBB) are discussed. Tracers are transported through the BBB into the brain, v...
journal_title:Molecular imaging and biology
pub_type: 杂志文章,评审
doi:10.1016/j.mibio.2004.06.008
更新日期:2004-09-01 00:00:00
abstract:PURPOSE:The transplantation of pancreatic islets is a promising cell replacement therapy for type 1 diabetes. Subcutaneous islet transplantation is currently under investigation as a means to circumvent problems associated with standard intra-hepatic islet transplantation. As modifications are being developed to improv...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-020-01560-2
更新日期:2020-11-02 00:00:00
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. ...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-020-01518-4
更新日期:2020-10-01 00:00:00
abstract:PURPOSE:Nowadays, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/X-ray computed tomography (CT) is considered the best available technique to in vivo determination of human BAT volume. The most used Hounsfield unit (HU) threshold for BAT quantification is from - 250 to - 50 HU. Therefore,...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-019-01381-y
更新日期:2020-04-01 00:00:00
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:Negative surgical margins (NSMs) have favorable prognostic implications in breast tumor resection surgery. Fluorescence image-guided surgery (FIGS) has the ability to delineate surgical margins in real time, potentially improving the completeness of tumor resection. We have recently developed indocyanine green ...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-019-01462-y
更新日期:2020-08-01 00:00:00
abstract:PURPOSE:Synapse loss is a hallmark of Alzheimer's disease (AD) and correlates with cognitive decline. The validation of a noninvasive in vivo imaging approach to quantify synapse would greatly facilitate our understanding of AD pathogenesis and assist drug developments for AD. As animal models of neurodegenerative and ...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-020-01567-9
更新日期:2020-11-30 00:00:00
abstract:PURPOSE:The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. PROCEDURES:Twenty Sprague Dawley male rats were administered with mul...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-020-01488-7
更新日期:2020-10-01 00:00:00
abstract::This paper demonstrates the application of mutual information based coregistration of radionuclide and magnetic resonance imaging (MRI) in an effort to use multimodality imaging for noninvasive localization of stem cells grafted in the infarcted myocardium in rats. Radionuclide imaging such as single photon emission c...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-006-0062-3
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:The present work was aimed at the formulation and evaluation of freeze-dried kits of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptides for the preparation of (68)Ga-labelled peptides for PET imaging of neuroendocrine tumours. The (68)GaCl3 was obtained from the locally produced nanoceria-...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-014-0719-2
更新日期:2014-08-01 00:00:00
abstract::Incidental adrenal lesions found on anatomic imaging are not uncommon. 2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) imaging is highly accurate in the differentiation of benign from malignant adrenal lesions, both in patients with proven malignancy and with adrenal lesions detected incidentall...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1016/s1536-1632(02)00018-5
更新日期:2002-10-01 00:00:00
abstract:PURPOSE:High-dose (HD) cytosine arabinoside (ara-C) is a major treatment in acute myeloblastic leukemia (AML) that can lead to cerebellar complications, although electroencephalogram, computed tomography, and magnetic resonance imaging remain normal. We conducted a prospective study to evaluate brain perfusion with sin...
journal_title:Molecular imaging and biology
pub_type: 临床试验,杂志文章
doi:10.1007/s11307-010-0409-7
更新日期:2011-08-01 00:00:00
abstract::The Commercial Innovation of the Year Award went to Emile Beaulieu of Photon etc. for their work. ...
journal_title:Molecular imaging and biology
pub_type: 已发布勘误
doi:10.1007/s11307-019-01457-9
更新日期:2020-02-01 00:00:00
abstract:PURPOSE:Evaluation of [68Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity. PROCEDURES:Tracer specificity of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was anal...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-019-01417-3
更新日期:2020-06-01 00:00:00
abstract:PURPOSE:Recent researches have demonstrated the value of using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study foc...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-018-1182-2
更新日期:2018-10-01 00:00:00
abstract:PURPOSE:The aim of this work is to investigate the impact of tissue classification in magnetic resonance imaging (MRI)-guided positron emission tomography (PET) attenuation correction (AC) for whole-body (WB) Patlak net uptake rate constant (Ki) imaging in PET/MRI studies. PROCEDURES:WB dynamic PET/CT data were acquir...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-019-01338-1
更新日期:2019-12-01 00:00:00
abstract::Erdheim-Chester disease (ECD) is a disseminated xanthogranulomatous infiltrative disease of unknown etiology due to infiltration of different organs and bones by foamy histiocytes. A 37-year-old male with cerebral and periorbital lesions was diagnosed with this rare disease and was evaluated with magnetic resonance im...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1016/j.mibio.2004.01.023
更新日期:2004-01-01 00:00:00
abstract:PURPOSE:[(18)F]Flumazenil, which has the advantage of a longer half-life than [(11)C]flumazenil, is well known for determining of the central benzodiazepine receptor concentrations. However, [(18)F]flumazenil has not been widely used because fluctuating and relatively low yields render automatic production insufficient...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-014-0738-z
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:Transplantation of a regenerative cell population derived from human subcutaneous adipose tissue (hASCs) for cardiac regeneration represents a promising therapy due to the capacity of these cells for proliferation and differentiation. Understanding the fate of injected hASCs would help to understand how hASCs w...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-010-0392-z
更新日期:2011-08-01 00:00:00
abstract:PURPOSE:This study aims to explore whether 4-(2S,4R)-[18F]fluoroglutamine (4-[18F]FGln) positron emission tomography (PET) imaging is helpful in identifying and monitoring MYCN-amplified neuroblastoma by enhanced glutamine metabolism. PROCEDURES:Cell uptake studies and dynamic small-animal PET studies of 4-[18F]FGln a...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-019-01330-9
更新日期:2019-12-01 00:00:00
abstract:PURPOSE:Cellular receptor targeted imaging agents present the potential to target extracellular molecular expression in cancerous lesions; however, the image contrast in vivo does not reflect the magnitude of overexpression expected from in vitro data. Here, the in vivo delivery and binding kinetics of epidermal growth...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-011-0503-5
更新日期:2012-08-01 00:00:00
abstract:PURPOSE:Antibodies form an important class of cancer therapeutics, and there is intense interest in using them for imaging applications in diagnosis and monitoring of cancer treatment. Despite the expanding body of knowledge describing pharmacokinetic and pharmacodynamic interactions of antibodies in vivo, discrepancie...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-010-0397-7
更新日期:2011-08-01 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:This study describes an imaging strategy based on glow stick chemistry to non-invasively image oxidative stress and reactive oxygen species (ROS) production in living animals. PROCEDURES:Upon stimulation, phagocytes produce toxic levels of ROS to kill engulfed microorganisms. The mitochondrial respiratory chai...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-014-0721-8
更新日期:2014-08-01 00:00:00
abstract:PURPOSE:The aim of this study is to generate a four-class magnetic resonance imaging (MRI)-based attenuation map (μ-map) for attenuation correction of positron emission tomography (PET) data of the head area using a novel combination of short echo time (STE)/Dixon-MRI and a dedicated image segmentation method. PROCEDU...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-015-0849-1
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:The purpose of this study was to determine the most useful parameter of dual-time-point 2-deoxy-2-[¹⁸F]fluoro-D: -glucose positron emission tomography/computed tomography (PET/CT) for detection of hepatic metastases in patients with colorectal cancer. PROCEDURES:Thirty-nine patients had undergone a dual-time-p...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-010-0394-x
更新日期:2011-06-01 00:00:00