scholarly journals There is a world beyond αvβ3-integrin: Multimeric ligands for imaging of the integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1 by positron emission tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katja Steiger ◽  
Neil Gerard Quigley ◽  
Tanja Groll ◽  
Frauke Richter ◽  
Maximilian Alexander Zierke ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Αvβ3 Integrin ◽  
Rgd Peptides ◽  
Rgd Sequence ◽  
Positron Emission ◽  
German Research ◽  
Integrin Ligands ◽  
Αvβ6 Integrin ◽  
Gallium 68 ◽  
Clinical Potential

Abstract Background In the context of nuclear medicine and theranostics, integrin-related research and development was, for most of the time, focused predominantly on 'RGD peptides' and the subtype αvβ3-integrin. However, there are no less than 24 known integrins, and peptides without the RGD sequence as well as non-peptidic ligands play an equally important role as selective integrin ligands. On the other hand, multimerization is a well-established method to increase the avidity of binding structures, but multimeric radiopharmaceuticals have not made their way into clinics yet. In this review, we describe how these aspects have been interwoven in the framework of the German Research Foundation's multi-group interdisciplinary funding scheme CRC 824, yielding a series of potent PET imaging agents for selective imaging of various integrin subtypes. Results The gallium-68 chelator TRAP was utilized to elaborate symmetrical trimers of various peptidic and non-peptidic integrin ligands. Preclinical data suggested a high potential of the resulting Ga-68-tracers for PET-imaging of the integrins α5β1, αvβ8, αvβ6, and αvβ3. For the first three, we provide some additional immunohistochemistry data in human cancers, which suggest several future clinical applications. Finally, application of αvβ3- and αvβ6-integrin tracers in pancreatic carcinoma patients revealed that unlike αvβ3-targeted PET, αvβ6-integrin PET is not characterized by off-target uptake and thus, enables a substantially improved imaging of this type of cancer. Conclusions Novel radiopharmaceuticals targeting a number of different integrins, above all, αvβ6, have proven their clinical potential and will play an increasingly important role in future theranostics.

scholarly journals [68Ga]Ga-DFO-c(RGDyK): Synthesis and Evaluation of Its Potential for Tumor Imaging in Mice

2021 ◽  
Vol 22 (14) ◽  
pp. 7391
Author(s):  
Sona Krajcovicova ◽  
Andrea Daniskova ◽  
Katerina Bendova ◽  
Zbynek Novy ◽  
Miroslav Soural ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Imaging ◽  
Ex Vivo ◽  
Cell Uptake ◽  
Αvβ3 Integrin ◽  
In Vitro Characterization ◽  
Positron Emission ◽  
Gallium 68

Angiogenesis has a pivotal role in tumor growth and the metastatic process. Molecular imaging was shown to be useful for imaging of tumor-induced angiogenesis. A great variety of radiolabeled peptides have been developed to target αvβ3 integrin, a target structure involved in the tumor-induced angiogenic process. The presented study aimed to synthesize deferoxamine (DFO)-based c(RGD) peptide conjugate for radiolabeling with gallium-68 and perform its basic preclinical characterization including testing of its tumor-imaging potential. DFO-c(RGDyK) was labeled with gallium-68 with high radiochemical purity. In vitro characterization including stability, partition coefficient, protein binding determination, tumor cell uptake assays, and ex vivo biodistribution as well as PET/CT imaging was performed. [68Ga]Ga-DFO-c(RGDyK) showed hydrophilic properties, high stability in PBS and human serum, and specific uptake in U-87 MG and M21 tumor cell lines in vitro and in vivo. We have shown here that [68Ga]Ga-DFO-c(RGDyK) can be used for αvβ3 integrin targeting, allowing imaging of tumor-induced angiogenesis by positron emission tomography.

scholarly journals Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider

2021 ◽  
Author(s):  
Michael Meisenheimer ◽  
Yury Saenko ◽  
Elisabeth Eppard
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Clinical Applications ◽  
Emission Tomography ◽  
Automated Synthesis ◽  
Production Route ◽  
Positron Emission ◽  
Purification Methods ◽  
Gallium 68 ◽  
Operator Safety

Gallium-68 was applied for positron emission tomography (PET) imaging already in the early beginnings of PET imaging. Today, with the introduction of PSMA-targeting tracers (e.g. PSMA-11, PSMA-617, and PSMA-I&T), the number of clinical applications of 68Ga-radiopharmaceuticals for diagnostic imaging has grown considerably. This development was initiated and supported already in the mid-2000s by the commercial availability of 68Ge/68Ga generators designed for clinical usage. This progression was accompanied by the development of several purification methods to generator eluate as well as sophisticated 68Ga-radiopharmaceuticals. Due to the 68Ga-rush, the need for implementation of gallium-68 (depending on production route) and its certain tracers into the pharmacopeia increased. Based on the specifications given by the pharmacopeia, interest focused on the development of automated synthesis systems, 99mTc-analog kits with regard to patient as well as operator safety.

scholarly journals PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides

2010 ◽  
Vol 38 (1) ◽  
pp. 128-137 ◽  
Author(s):  
Ingrid Dijkgraaf ◽  
Cheng-Bin Yim ◽  
Gerben M. Franssen ◽  
Robert C. Schuit ◽  
Gert Luurtsema ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Αvβ3 Integrin ◽  
Integrin Expression ◽  
Rgd Peptides

scholarly journals A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2866 ◽  
Author(s):  
Cyril Fersing ◽  
Ahlem Bouhlel ◽  
Christophe Cantelli ◽  
Philippe Garrigue ◽  
Vincent Lisowski ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Metal Chelate ◽  
Comprehensive Overview ◽  
Covalent Bonds ◽  
Positron Emission ◽  
One Step ◽  
Evaluation Stage ◽  
Gallium 68 ◽  
Pet Probes ◽  
18F Fluoride

Due to its ideal physical properties, fluorine-18 turns out to be a key radionuclide for positron emission tomography (PET) imaging, for both preclinical and clinical applications. However, usual biomolecules radiofluorination procedures require the formation of covalent bonds with fluorinated prosthetic groups. This drawback makes radiofluorination impractical for routine radiolabeling, gallium-68 appearing to be much more convenient for the labeling of chelator-bearing PET probes. In response to this limitation, a recent expansion of the 18F chemical toolbox gave aluminum [18F]fluoride chemistry a real prominence since the late 2000s. This approach is based on the formation of an [18F][AlF]2+ cation, complexed with a 9-membered cyclic chelator such as NOTA, NODA or their analogs. Allowing a one-step radiofluorination in an aqueous medium, this technique combines fluorine-18 and non-covalent radiolabeling with the advantage of being very easy to implement. Since its first reports, [18F]AlF radiolabeling approach has been applied to a wide variety of potential PET imaging vectors, whether of peptidic, proteic, or small molecule structure. Most of these [18F]AlF-labeled tracers showed promising preclinical results and have reached the clinical evaluation stage for some of them. The aim of this report is to provide a comprehensive overview of [18F]AlF labeling applications through a description of the various [18F]AlF-labeled conjugates, from their radiosynthesis to their evaluation as PET imaging agents.

Usefulness of positron emission tomography for differentiating gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system

2020 ◽  
Vol 133 (4) ◽  
pp. 1010-1019 ◽  
Author(s):  
Hiroaki Takei ◽  
Jun Shinoda ◽  
Soko Ikuta ◽  
Takashi Maruyama ◽  
Yoshihiro Muragaki ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Who Classification ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
World Health ◽  
Pet Tracers ◽  
Positron Emission ◽  
Significant Difference ◽  
The Mean

OBJECTIVEPositron emission tomography (PET) is important in the noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 WHO classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification). Here, the authors investigated the relationship between uptake of 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) on PET imaging and isocitrate dehydrogenase (IDH) status (wild-type [IDH-wt] or mutant [IDH-mut]) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification.METHODSIn total, 105 patients with newly diagnosed cerebral gliomas (6 diffuse astrocytomas [DAs] with IDH-wt, 6 DAs with IDH-mut, 7 anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, 5 GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake value (SUV) of the tumor/mean SUV of normal cortex (T/N) ratios for MET, CHO, and FDG were calculated, and the mean T/N ratios of DA, AA, and GBM with IDH-wt and IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the 3 PET tracers.RESULTSThere were significant differences in the mean T/N ratios for all 3 PET tracers between the IDH-wt and IDH-mut groups of all histological classifications (p < 0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all 3 PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all 3 PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p < 0.01). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that in the IDH-mut group for both MET (p = 0.034) and CHO (p = 0.01). However, there was no significant difference in the ratio for FDG.CONCLUSIONSPET imaging using MET, CHO, and FDG was suggested to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.

Role of Positron Emission Tomography for Central Nervous System Involvement in Systemic Autoimmune Diseases: Status and Perspectives

2018 ◽  
Vol 25 (26) ◽  
pp. 3096-3104 ◽  
Author(s):  
Daniele Mauro ◽  
Gaetano Barbagallo ◽  
Salvatore D`Angelo ◽  
Pasqualina Sannino ◽  
Saverio Naty ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Central Nervous System ◽  
Nervous System ◽  
Autoimmune Diseases ◽  
Pet Imaging ◽  
Emission Tomography ◽  
Cns Involvement ◽  
Systemic Autoimmune Diseases ◽  
Positron Emission

In the last years, an increasing interest in molecular imaging has been raised by the extending potential of positron emission tomography [PET]. The role of PET imaging, originally confined to the oncology setting, is continuously extending thanks to the development of novel radiopharmaceutical and to the implementation of hybrid imaging techniques, where PET scans are combined with computed tomography [CT] or magnetic resonance imaging[MRI] in order to improve spatial resolution. Early preclinical studies suggested that 18F–FDG PET can detect neuroinflammation; new developing radiopharmaceuticals targeting more specifically inflammation-related molecules are moving in this direction. Neurological involvement is a distinct feature of various systemic autoimmune diseases, i.e. Systemic Lupus Erythematosus [SLE] or Behcet’s disease [BD]. Although MRI is largely considered the gold-standard imaging technique for the detection of Central Nervous System [CNS] involvement in these disorders. Several patients complain of neuropsychiatric symptoms [headache, epilepsy, anxiety or depression] in the absence of any significant MRI finding; in such patients the diagnosis relies mainly on clinical examination and often the role of the disease process versus iatrogenic or reactive forms is doubtful. The aim of this review is to explore the state-of-the-art for the role of PET imaging in CNS involvement in systemic rheumatic diseases. In addition, we explore the potential role of emerging radiopharmaceutical and their possible application in aiding the diagnosis of CNS involvement in systemic autoimmune diseases.

PET Imaging of Adenosine Receptors in Diseases

2019 ◽  
Vol 19 (16) ◽  
pp. 1445-1463 ◽  
Author(s):  
Jindian Li ◽  
Xingfang Hong ◽  
Guoquan Li ◽  
Peter S. Conti ◽  
Xianzhong Zhang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Adenosine Receptors ◽  
Neurological Diseases ◽  
G Protein Coupled Receptors ◽  
Extracellular Adenosine ◽  
Positron Emission ◽  
Imaging Probes ◽  
Pet Probes ◽  
Cancer And Inflammation ◽  
G Protein Coupled

Adenosine receptors (ARs) are a class of purinergic G-protein-coupled receptors (GPCRs). Extracellular adenosine is a pivotal regulation molecule that adjusts physiological function through the interaction with four ARs: A1R, A2AR, A2BR, and A3R. Alterations of ARs function and expression have been studied in neurological diseases (epilepsy, Alzheimer’s disease, and Parkinson’s disease), cardiovascular diseases, cancer, and inflammation and autoimmune diseases. A series of Positron Emission Tomography (PET) probes for imaging ARs have been developed. The PET imaging probes have provided valuable information for diagnosis and therapy of diseases related to alterations of ARs expression. This review presents a concise overview of various ARs-targeted radioligands for PET imaging in diseases. The most recent advances in PET imaging studies by using ARs-targeted probes are briefly summarized.

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