Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes

Cornelissen, Bart

doi:10.1002/jlcr.3152

Cited by 27 publications

(19 citation statements)

References 110 publications

(130 reference statements)

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“…Cellular targeting was mainly directed to membrane receptors, because of their abundant expression and relative accessibility. However, the majority of potential cancer cell targets reside intracellularly ( Cornelissen, 2014 ). Specific subcellular targeting of theranostic probes may therefore not only have an impact on cancer cell kill, but also on imaging.…”

Section: Methods To Detect the Spatial Distribution Of Radionuclidesmentioning

confidence: 99%

“…Strategies involve direct targeting of the DNA, sex steroid receptors (SSRs; androgen, estrogen), and nuclear trafficking cell surface receptors (EGFR, HER2). Furthermore, subnuclear targeting has been achieved by binding nuclear proteins (γH2AX, telomerase), and the nucleolus ( Cornelissen, 2014 ). The following section summarizes recent advances in the area of targeting subcellular compartments ( Table 3 ).…”

Section: Subcellular Targets For Radionuclide Therapymentioning

confidence: 99%

“…The nucleus not only contains DNA, but also harbors many proteins that are essential for genome expression and integrity ( Cornelissen, 2014 ). Targeting these proteins can be exploited in TRT.…”

Section: Subcellular Targets For Radionuclide Therapymentioning

confidence: 99%

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Subcellular Targeting of Theranostic Radionuclides

et al. 2018

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The last decade has seen rapid growth in the use of theranostic radionuclides for the treatment and imaging of a wide range of cancers. Radionuclide therapy and imaging rely on a radiolabeled vector to specifically target cancer cells. Radionuclides that emit β particles have thus far dominated the field of targeted radionuclide therapy (TRT), mainly because the longer range (μm–mm track length) of these particles offsets the heterogeneous expression of the molecular target. Shorter range (nm–μm track length) α- and Auger electron (AE)-emitting radionuclides on the other hand provide high ionization densities at the site of decay which could overcome much of the toxicity associated with β-emitters. Given that there is a growing body of evidence that other sensitive sites besides the DNA, such as the cell membrane and mitochondria, could be critical targets in TRT, improved techniques in detecting the subcellular distribution of these radionuclides are necessary, especially since many β-emitting radionuclides also emit AE. The successful development of TRT agents capable of homing to targets with subcellular precision demands the parallel development of quantitative assays for evaluation of spatial distribution of radionuclides in the nm–μm range. In this review, the status of research directed at subcellular targeting of radionuclide theranostics and the methods for imaging and quantification of radionuclide localization at the nanoscale are described.

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Section: Methods To Detect the Spatial Distribution Of Radionuclidesmentioning

confidence: 99%

Section: Subcellular Targets For Radionuclide Therapymentioning

confidence: 99%

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Subcellular Targeting of Theranostic Radionuclides

et al. 2018

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“…[6][7][8] Nuclear medicine has been a revolutionary invention in the field of diagnostic imaging because it is noninvasive and facilitates continuous monitoring of disease progression or treatment response. 9,10 Moreover, the imaging modalities in nuclear medicine, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) can quantify receptor density and molecular target expression in patients, thus becoming a useful tool in drug development. [10][11][12] Previous studies have reported imaging agents, including radiolabeled protein, 13,14 aptamer, 15 affibody molecules, 16,17 and peptide 18,19 that target the extracellular parts of PDGFRβ.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of radioiodinated 1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging

Effendi

Ogawa

Mishiro

et al. 2017

Bioorganic & Medicinal Chemistry

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Platelet-derived growth factor receptor β (PDGFRβ) is a transmembrane tyrosine kinase receptor and it is upregulated in various malignant tumors. Radiolabeled PDGFRβ inhibitors can be a convenient tool for the imaging of tumors overexpressing PDGFRβ. In this study, [I]-1-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl}piperidin-4-amine ([I]IIQP) and [I]-N-3-iodobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([I]IB-IQP) were designed and synthesized, and their potential as PDGFRβ imaging agents was evaluated. In cellular uptake experiments, [I]IIQP and [I]IB-IQP showed higher uptake by PDGFRβ-positive cells than by PDGFRβ-negative cells, and the uptake in PDGFRβ-positive cells was inhibited by co-culture with PDGFRβ ligands. The biodistribution of both radiotracers in normal mice exhibited hepatobiliary excretion as the main route. In mice inoculated with BxPC3-luc (PDGFRβ-positive), the tumor uptake of radioactivity at 1h after the injection of [I]IIQP was significantly higher than that after the injection of [I]IB-IQP. These results indicated that [I]IIQP can be a suitable PDGFRβ imaging agent. However, further modification of its structure will be required to obtain a more appropriate PDGFRβ-targeted imaging agent with a higher signal/noise ratio.

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“…Therefore, Auger electrons can induce various types of DNA damage such as multiple double-strand breaks (DSB) when they are localized in close proximity to the DNA [3–6]. The diagnostic and therapeutic use of Auger emitters, especially 125 I ( 123 I) or 111 In, has been widely discussed [7–10]. In addition to these prominent Auger emitters, 99m Tc emits almost five low energy electrons with a range of less than 200 nm [1, 11] and initial tests demonstrated that it might be possible to use 99m Tc for Auger electron therapy [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Direct and Auger Electron-Induced, Single- and Double-Strand Breaks on Plasmid DNA Caused by 99mTc-Labeled Pyrene Derivatives and the Effect of Bonding Distance

et al. 2016

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It is evident that 99mTc causes radical-mediated DNA damage due to Auger electrons, which were emitted simultaneously with the known γ-emission of 99mTc. We have synthesized a series of new 99mTc-labeled pyrene derivatives with varied distances between the pyrene moiety and the radionuclide. The pyrene motif is a common DNA intercalator and allowed us to test the influence of the radionuclide distance on damages of the DNA helix. In general, pUC 19 plasmid DNA enables the investigation of the unprotected interactions between the radiotracers and DNA that results in single-strand breaks (SSB) or double-strand breaks (DSB). The resulting DNA fragments were separated by gel electrophoresis and quantified by fluorescent staining. Direct DNA damage and radical-induced indirect DNA damage by radiolysis products of water were evaluated in the presence or absence of the radical scavenger DMSO. We demonstrated that Auger electrons directly induced both SSB and DSB in high efficiency when 99mTc was tightly bound to the plasmid DNA and this damage could not be completely prevented by DMSO, a free radical scavenger. For the first time, we were able to minimize this effect by increasing the carbon chain lengths between the pyrene moiety and the 99mTc nuclide. However, a critical distance between the 99mTc atom and the DNA helix could not be determined due to the significantly lowered DSB generation resulting from the interaction which is dependent on the type of the 99mTc binding motif. The effect of variable DNA damage caused by the different chain length between the pyrene residue and the Tc-core as well as the possible conformations of the applied Tc-complexes was supplemented with molecular dynamics (MD) calculations. The effectiveness of the DNA-binding 99mTc-labeled pyrene derivatives was demonstrated by comparison to non-DNA-binding 99mTcO4–, since nearly all DNA damage caused by 99mTcO4– was prevented by incubating with DMSO.

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Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes

Cited by 27 publications

References 110 publications

Subcellular Targeting of Theranostic Radionuclides

Subcellular Targeting of Theranostic Radionuclides

Synthesis and evaluation of radioiodinated 1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging

Direct and Auger Electron-Induced, Single- and Double-Strand Breaks on Plasmid DNA Caused by 99mTc-Labeled Pyrene Derivatives and the Effect of Bonding Distance

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