Abstract:
:Over the last years Gallium-68 ((68)Ga) has received tremendous attention for labeling of radiopharmaceuticals for positron emission tomography (PET). (68)Ga labeling of biomolecules is currently based on bifunctional chelators containing aminocarboxylates (mainly DOTA and NOTA). We have recently shown that cyclic peptide siderophores have very good complexing properties for (68)Ga resulting in high specific activities and excellent metabolic stabilities, in particular triacetylfusarinine-C (TAFC). We postulated, that, starting from its deacetylated form (Fusarinine-C (FSC)) trimeric bioconjugates are directly accessible to develop novel targeting peptide based (68)Ga labeled radiopharmaceuticals. As proof of principle we report on the synthesis and (68)Ga-radiolabeling of a trimeric FSC-RGD conjugate, [(68)Ga]FSC-(RGD)3, targeting αvβ3 integrin, which is highly expressed during tumor-induced angiogenesis. Synthesis of the RGD peptide was carried out applying solid phase peptide synthesis (SPPS), followed by the coupling to the siderophore [Fe]FSC via in situ activation using HATU/HOAt and DIPEA. Subsequent demetalation allowed radiolabeling of FSC-(RGD)3 with (68)Ga. The radiolabeling procedure was optimized regarding peptide amount, reaction time, temperature as well buffer systems. For in vitro evaluation partition coefficient, protein binding, serum stability, αvβ3 integrin binding affinity, and tumor cell uptake were determined. For in vitro tests as well as for the biodistribution studies αvβ3 positive human melanoma M21 and αvβ3 negative M21-L cells were used. [(68)Ga]FSC-(RGD)3 was prepared with high radiochemical yield (>98%). Distribution coefficient was -3.6 revealing a hydrophilic character, and an IC50 value of 1.8±0.6 nM was determined indicating a high binding affinity for αvβ3 integrin. [(68)Ga]FSC-(RGD)3 was stable in PBS (pH7.4), FeCl3- and DTPA-solution as well as in fresh human serum at 37°C for 2hours. Biodistribution assay confirmed the receptor specific uptake found in vitro. Uptake in the αvβ3 positive tumor was 4.3% ID/g 60min p.i. which was 3-fold higher than the monomeric [(68)Ga]NODAGA-RGD. Tumor to blood ratio of approx. 8 and tumor to muscle ratio of approx. 7 were observed. [(68)Ga]FSC-(RGD)3 serves as an example for the feasibility of a novel class of bifunctional chelators based on cyclic peptide siderophores and shows excellent targeting properties for αvβ3 integrin in vivo for imaging tumor-induced neovascularization.
journal_name
Nucl Med Bioljournal_title
Nuclear medicine and biologyauthors
Knetsch PA,Zhai C,Rangger C,Blatzer M,Haas H,Kaeopookum P,Haubner R,Decristoforo Cdoi
10.1016/j.nucmedbio.2014.10.001subject
Has Abstractpub_date
2015-02-01 00:00:00pages
115-22issue
2eissn
0969-8051issn
1872-9614pii
S0969-8051(14)00515-0journal_volume
42pub_type
杂志文章abstract::A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand (123)I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clin...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(03)00046-5
更新日期:2003-08-01 00:00:00
abstract:INTRODUCTION:As the use of metallic radionuclides increases, so does the demand for a simple production method. In this study, we demonstrated an in situ target processing concept for automated metallic radionuclide production without the use of any robotic device. METHODS:An alumina ceramic vessel for a vertical irra...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2012.05.010
更新日期:2012-11-01 00:00:00
abstract::With [11C]raclopride,[11C]nemonapride and [11C]N-methylspiperone, degeneration of dopamine D2-like receptors in the unilaterally quinolinic acid-lesioned rats was evaluated by positron emission tomography (PET) and ex vivo and in vitro autoradiography. PET showed a decreased uptake of [11C]raclopride in the lesioned s...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(01)00307-9
更新日期:2002-04-01 00:00:00
abstract::Two photolabile heterobifunctional O-nitrobenzyl reagents were used to modify B72.3 monoclonal antibody followed by immobilization on a solid support. Antibody was labeled with 99mTc and then cleaved from the resin on irradiation with light of peak intensity at 365 nm. The antibody was restored unmodified after cleava...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(94)00147-c
更新日期:1995-07-01 00:00:00
abstract::Antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. (99m)Tc-UBI labeled by a direct method has shown high in vitro and in vivo stability, specific uptake at the site of infection, rapid background clearance, minimal accumulation in non...
journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1016/j.nucmedbio.2003.10.005
更新日期:2004-04-01 00:00:00
abstract::Deuteron-induced nuclear reactions for generation of no-carrier-added (NCA) Lu isotopes were investigated using the stacked-foil activation technique on natural Yb targets at energies up to Ed=18.18MeV. The decay curve of ¹⁷⁷Yb, the growth curve of the cumulative (direct and indirect) and the direct production of (177...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2014.02.007
更新日期:2014-05-01 00:00:00
abstract::Positron-emission tomography (PET) provides potential in neuropsychiatric drug development by expanding knowledge of drug action in the living human brain and reducing time consumption and costs. The 5-hydroxytryptamine(1A) (5-HT(1A)) receptor is of central interest as a target for the treatment of anxiety, depression...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(00)00121-9
更新日期:2000-07-01 00:00:00
abstract:INTRODUCTION:Rodent models are extensively used to assess the biochemical and physiological changes associated with aging. They play a major role in the development of therapies for age-related pathologies such as Parkinson's disease. To validate the usefulness of these animal models in aging or age-related disease res...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2014.12.020
更新日期:2015-04-01 00:00:00
abstract::Synthesis and preliminary biological evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)-guanine ([18F]FHBG) is reported. 9-(4-Hydroxy-3-hydroxymethylbutyl)-guanine (penciclovir) 4 was converted to 9-[N2, O-bis-(methoxytrityl)-3-(tosylmethybutyl)]guanine 7 by treatment with methoxytrityl chloride followed by tosylat...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(97)00160-1
更新日期:1998-04-01 00:00:00
abstract::A positron-emitter labeled radioligand for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, [(11)C]L-703,717, was examined for its ability to penetrate the brain in animals by simultaneous use with drugs having high-affinity separate binding sites on human serum albumin. [(11)C]L-703,717 has poor ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(00)00096-2
更新日期:2000-05-01 00:00:00
abstract::We have investigated whether [186Re]-labeled chimeric monoclonal antibody 323/A3 (MAb c-323/A3) is as effective as [186Re]-labeled mouse 323/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xenografts OVCAR-3 and FMa. [186Re] was conjugated to MAbs with the use of the chelate S-benzoylmercaptoacetyltrigl...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(97)00154-6
更新日期:1998-01-01 00:00:00
abstract::Brofaromine (4-5(-methoxy-7-bromobenzofuranyl)-2-piperidine-HCl) is a potent and selective inhibitor of monoamine oxidase (MAO) A. Two methods for its synthesis and a preliminary positron emission tomography (PET) evaluation in monkey brain are described. The first method, at low carrier concentration of CO2, consiste...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)02051-9
更新日期:1996-04-01 00:00:00
abstract::The ability to measure blood flow to tumors non-invasively may be of importance in monitoring tumor therapies, assessing drug delivery, and understanding tumor physiology. Of all the radiotracer methods that have been proposed to measure tumor blood flow, the method based on labeled water-H(2)(15)O-may be the most app...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章,评审
doi:10.1016/s0969-8051(00)00136-0
更新日期:2000-10-01 00:00:00
abstract::We compared the influence of three different catechol-O-methyltransferase (COMT) inhibitors (CGP 28014, OR-611 and Ro 40-7592) on the metabolism of no-carrier-added (NCA) 6-[18F]fluoro-L-dopa (6-FDOPA) in one Rhesus monkey. All three COMT inhibitors improved 6-FDOPA availability in plasma, increased the specific uptak...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)00032-s
更新日期:1995-10-01 00:00:00
abstract::In the quantitative studies of presynaptic dopamine metabolism by PET with 6-[18F]fluoro-L-dopa (6-[18F]FDOPA), metabolic analysis in the plasma is required to determine the precise input function because of susceptibility of the compound to peripheral metabolism. In this study, we prepared 6-[18F]-fluoro-O-pivaloyl-L...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)02083-7
更新日期:1996-04-01 00:00:00
abstract:INTRODUCTION:We measured the tiagabine-induced enhancement of the GABAA receptor's affinity for benzodiazepine ligands ("GABA shift") using [18F]flumazenil (FMZ) PET with preclinical application of bolus plus constant infusion (B/I). Differences in quantified results of [18F]FMZ binding were compared to that of [18F]FM...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2016.11.003
更新日期:2017-02-01 00:00:00
abstract::Dual probe microdialysis was employed in intact rat brain to investigate the effect of intrastriatal perfusion with selective dopamine D1 and D2 receptor agonists and with c-fos antisense oligonucleotide on (a) local GABA release in the striatum; (b) the internal segment of the globus pallidus and the substantia nigra...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(98)00066-3
更新日期:1998-11-01 00:00:00
abstract:OBJECTIVES:To evaluate the effectiveness of PET in differentiating malignant from benign pancreatic cystic tumors. METHODS:Between 2009 and 2010, all patients with pancreatic cystic tumors who had PET, triple phase contrast computed tomography (CT) and endoscopic ultrasound (EUS) were reviewed. Clinicopathological cha...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2012.03.005
更新日期:2012-10-01 00:00:00
abstract:BACKGROUND:Cu-diacetyl-bis(N4-methylthiosemicarbazone) [Cu-ATSM], although excellent for oncology applications, may not be suitable for delineating cardiovascular or neurological hypoxia. For this reason, new Cu hypoxia positron emission tomography (PET) imaging agents are being examined to search for a higher selectiv...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2004.10.004
更新日期:2005-02-01 00:00:00
abstract::We have synthesized N-(6-18F-fluorohexyl)-N-methylpropargylamine (18F-FHMP) as a positron emission tomography (PET) radiotracer for monoamine oxidase B (MAO-B). The radiosynthesis was carried out by a fluorine-for-bromine substitution in 30-40% radiochemical yield in specific activities of 1-2 Ci/micromol. Selectivity...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(98)00061-4
更新日期:1999-01-01 00:00:00
abstract:INTRODUCTION:Image-derived input functions (IDIFs) represent a promising non-invasive alternative to arterial blood sampling for quantification in positron emission tomography (PET) studies. However, routine applications in patients and longitudinal designs are largely missing despite widespread attempts in healthy sub...
journal_title:Nuclear medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1016/j.nucmedbio.2012.12.011
更新日期:2013-04-01 00:00:00
abstract::A novel approach for the combinatorial synthesis of backbone-derived metal-cyclic peptide libraries is presented. In this approach the metalo-cyclic peptides are prepared from their linear precursors through complexation of a metal atom via two hemi-chelating arms located on the peptide backbone. Thus, cyclization and...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2004.08.007
更新日期:2005-01-01 00:00:00
abstract::A no-carrier-added, high specific activity synthesis of [11C-methyl]-thymidine is reported. Reaction of 3'. 5'-O-bis-(tetrahydropyramyl)-5-bromo-2'-deoxyuridine with n-butylithium produced a diamion which was alkylated with [11C]-methyl iodide, and on subsequent hydrolysis, yielded [IIC-methyl]-thymidine. The labeled ...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/0969-8051(95)00027-u
更新日期:1995-08-01 00:00:00
abstract::We attempted to measure the regional metabolic rate of glucose (MRglc) in sliced spinal cords in vitro. The thoracic spinal cord of a mature Wister rat was cut into 400-mum slices in oxygenated and cooled (1-4 degrees C) Krebs-Ringer solution. After at least 60 min of preincubation, the spinal cord slices were transfe...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2008.11.011
更新日期:2009-02-01 00:00:00
abstract:INTRODUCTION:Dysregulation of the hepatocyte growth factor (HGF)/MET pathway has been implicated in various cancers. Rilotumumab is an investigational, fully human monoclonal antibody that binds and neutralizes HGF. The purpose of this study was to evaluate the efficacy of rilotumumab in a U-87 MG mouse xenograft tumor...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2013.01.004
更新日期:2013-05-01 00:00:00
abstract:INTRODUCTION:Severe brain hypoxia in the territory of the occluded artery is a key feature of ischemic stroke. This region can be imaged using positron emission tomography (PET) and the standard hypoxia radiotracer (18)F-fluoromisonidazole ((18)F-FMISO). However, the utility of (18)F-FMISO is limited by its slow accumu...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2012.11.012
更新日期:2013-04-01 00:00:00
abstract:INTRODUCTION:We examined whether the amino acid PET tracers, trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) and (11)C-methyl-l-methionine ((11)C-Met), are suitable for detecting early responses to combination therapies including temozolomide (TMZ), interferon-β (IFN), and bevacizumab (Bev) in...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/j.nucmedbio.2015.01.008
更新日期:2015-07-01 00:00:00
abstract::To improve standardization in analytical reagents we investigated Chloramine-T radioiodination (125I) of several biomolecules based on the use of a single amount of the oxidizing agent Chloramine-T as the limiting reagent being exhausted during the course of the reaction. Whenever the labeling yield resulted in less t...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(01)00261-x
更新日期:2001-11-01 00:00:00
abstract::ABSTRACT. The aim of the present study was to investigate the lymphatic cardiac circulation in an experimental model of ischemia plus reperfusion in mongrel dogs (Canis familiaris L). As radiotracer we used 0.2-0.25 ml (111 MBq) of 99mTc-Re2S7 colloid (+/-10 microm), injected subcapsullary below the second diagonal of...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(98)00037-7
更新日期:1998-10-01 00:00:00
abstract::Packed capillary liquid chromatography with electrospray mass spectrometry was used for direct determination of the specific radioactivity by calculation of isotope ratios between the (76)Br- and (79)Br-labeled analogues of N-((3-aminomethyl)benzyl)-4-bromobenzamide. Using 20 microL injections on packed capillary colu...
journal_title:Nuclear medicine and biology
pub_type: 杂志文章
doi:10.1016/s0969-8051(00)00159-1
更新日期:2000-11-01 00:00:00