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Pharmaceuticals
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Radiopharmaceutical Chemistry between Imaging and Radioendotherapy
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Radiopharmaceutical Chemistry between Imaging and Radioendotherapy

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (15 December 2013) | Viewed by 133245

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Klaus Kopka

E-Mail Website
Guest Editor
Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, 01328 Dresden, Germany
Interests: radiopharmaceutical drug development; radiopharmaceutical sciences; medicinal radiochemistry; radionuclide theranostics; targeted endoradiotherapy; noninvasive molecular imaging; PET; SPECT
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The journal “Pharmaceuticals” is planning to publish a special issue covering the topic “Radiopharmaceutical Chemistry between Imaging and Radioendotherapy” and I am cordially inviting you to contribute an article to this volume.

Positron emission tomography (PET), single photon emission computed tomography (SPECT), and the combined imaging modalities realised in the en-vogue hybrid technologies PET/CT and PET/MR represent the state-of-the-art diagnostic imaging technologies in nuclear medicine which are used for the highly sensitive non-invasive imaging of biological processes at the subcellular and molecular level in a respective patient for the visualisation of rather early disease states or for early inspection of treatment response after chemotherapy, radiation- or radioendotherapy.

Radiolabelled molecules, bearing a “radioactive lantern”, function as so called Radiopharmaceuticals which have to be compliant with the pharmaceuticals act, and can be termed as “food” of nuclear medicine. In general, the specialised field Radiopharmaceutical Chemistry focusses on the development, synthesis and radiolabelling of aforementioned “food”, such as small molecules, biotechnology-derived antibodies or (cyclised) (oligo)peptides which are used to address clinically relevant biological “downstream” targets such as receptors, enzymes, transport systems and others. Addressing “upstream” targets such as DNA- and RNA-fragments using corresponding radioactive substrates represents a further feasible strategy.

Originally, Radiopharmaceutical Chemistry descends from radiochemistry and radiopharmacy as well as nuclear chemistry and uses methods finally aiming at the production of radioactive substances for human application which are essential for non-invasive in vivo imaging by means of the aforementioned scintigraphic methods PET or SPECT.

The cornerstone for applicable radiochemistry in nuclear medicine was set by the Hungarian chemist George Charles de Hevesy who received the Nobel Prize in 1943 for his work on the radioindicator principle. This principle is based on the idea that the absolute amount of the administered substance is below the dose needed to induce a pharmacodynamic effect. Nowadays, a radioactive substance that can be traced in vivo as it moves through the living organism is termed radiotracer or radiopharmaceutical. As mentioned above, the biodistribution of radiopharmaceuticals is measured non-invasively reflecting functional or molecular disorders without pharmacologically affecting the organism.

In the era of personalised medicine the diagnostic potential of radiopharmaceuticals is directly linked to a subsequent individual therapeutic approach called radioendotherapy. Depending on the “radioactive lantern” (gamma or particle emitter) used for radiolabelling of the respective tracer molecule, the field Radiopharmaceutical Chemistry can contribute to the set-up of an in vivo “theranostic” approach especially in tumour patients by offering tailor-made (radio)chemical entities labelled either with a diagnostic or a therapeutic radionuclide.

To succeed in the design of targeted high-affinity radiopharmaceuticals that can measure the alteration of receptors serving at the same time as biological targets for individualised radioendotherapy several aspects need to be considered: (i) reasonable pharmacological behaviour (especially pharmacokinetics adjusted to the physical half-life of the used radionuclide), (ii) ability to penetrate and cross biological membranes, (iii) usage of chemical as well as biological amplification strategies (e.g. pretargeting, biological trapping of converted ligands, change of the physicochemical behaviour of the radiopharmaceutical after target interaction, combination with biotransporters and heterodimer approaches), (iv) availability of radiopharmaceuticals with high specific activities and in vivo stability.

I would like you to share your contributions to the advances and opportunities in this highly recognised field Radiopharmaceutical Chemistry located between personalised non-invasive imaging and radioendotherapy for this special issue. Areas of interest include:

  • Feasible radionuclides and their production for direct or indirect radiolabelling of diagnostic and therapeutic radiopharmaceuticals including usage of prosthetic groups/radiosynthons,
  • Small (non-peptide) molecule-derived radiopharmaceuticals (PET and SPECT),
  • Biotechnology-derived radiopharmaceuticals (e.g. antibodies and derivatives thereof, fragments, affibodies, diabodies, (oligo)peptides) (PET and SPECT),
  • in vivo targeting strategies by chemical modification considering maintained target specificity and improved pharmacokinetics (e.g. SAR studies on lead structures, multimerisation yes or no, influence of linkers/spacers and chelators, molecular transporters, heterodimerisation),
  • Comparison of preclinical and clinical in vivo evaluations of respective radiotracers/radiopharmaceuticals (e.g. small-animal PET vs. human PET),
  • Examples of radiopharmaceuticals in oncology: in vivo “theranostic” approaches.

Prof. Dr. Klaus Kopka
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

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Editorial

Jump to: Research, Review

1751 KiB  
Editorial
Pharmaceuticals—Special Issue on Radiopharmaceutical Chemistry between Imaging and Endoradiotherapy
by Klaus Kopka
Pharmaceuticals 2014, 7(7), 839-849; https://doi.org/10.3390/ph7070839 - 16 Jul 2014
Cited by 1 | Viewed by 9086
Abstract
The fields of molecular biology, immunology and genetics have generated many important developments that advance the understanding of the induction and progression of oncological, cardiological and neurological diseases as well as the identification of disease-associated molecules and drugs that specifically target diseased cells [...] Read more.
The fields of molecular biology, immunology and genetics have generated many important developments that advance the understanding of the induction and progression of oncological, cardiological and neurological diseases as well as the identification of disease-associated molecules and drugs that specifically target diseased cells during therapy. These insights have triggered the development of targeted radiopharmaceuticals which open up a new dimension of radiopharmaceutical sciences in nuclear medicine. Radiopharmaceuticals, also called radiotracers, are radiolabelled molecules, bearing a “radioactive lantern”, and used as molecular probes to address clinically relevant biological targets such as receptors, enzymes, transport systems and others. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) realised in the en-vogue hybrid technologies PET/CT, SPECT/CT and PET/MRI represent the state-of-the-art diagnostic imaging technologies in nuclear medicine which are used to follow the trace of the administered radiopharmaceutical noninvasively thereby in vivo visualising and assessing biological processes at the subcellular and molecular level in a highly sensitive manner. In this connexion novel radiopharmaceuticals for the noninvasive molecular imaging of early disease states and monitoring of treatment responses in vivo by means of PET/CT, SPECT/CT and PET/MRI are indispensable prerequisites to further advance and strengthen the unique competence of radiopharmaceutical sciences. In the era of personalised medicine the diagnostic potential of radiopharmaceuticals is directly linked to a subsequent individual therapeutic approach called endoradiotherapy. Depending on the “radioactive lantern” (gamma or particle emitter) used for radiolabelling of the respective tracer molecule, the field of Radiopharmaceutical Chemistry can contribute to the set-up of an “in vivo theranostic” approach especially in tumour patients by offering tailor-made (radio)chemical entities labelled either with a diagnostic or a therapeutic radionuclide. [...] Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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Research

Jump to: Editorial, Review

1452 KiB  
Article
Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer
by Matthias Eder, Oliver Neels, Miriam Müller, Ulrike Bauder-Wüst, Yvonne Remde, Martin Schäfer, Ute Hennrich, Michael Eisenhut, Ali Afshar-Oromieh, Uwe Haberkorn and Klaus Kopka
Pharmaceuticals 2014, 7(7), 779-796; https://doi.org/10.3390/ph7070779 - 30 Jun 2014
Cited by 320 | Viewed by 20792
Abstract
The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA) has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability [...] Read more.
The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA) has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective 68Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx) pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [68Ga]Ga-PSMA-HBED-CC. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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489 KiB  
Article
A Bombesin-Shepherdin Radioconjugate Designed for Combined Extra- and Intracellular Targeting
by Christiane A. Fischer, Sandra Vomstein and Thomas L. Mindt
Pharmaceuticals 2014, 7(6), 662-675; https://doi.org/10.3390/ph7060662 - 27 May 2014
Cited by 8 | Viewed by 7403
Abstract
Radiolabeled peptides which target tumor-specific membrane structures of cancer cells represent a promising class of targeted radiopharmaceuticals for the diagnosis and therapy of cancer. A potential drawback of a number of reported radiopeptides is the rapid washout of a substantial fraction of the [...] Read more.
Radiolabeled peptides which target tumor-specific membrane structures of cancer cells represent a promising class of targeted radiopharmaceuticals for the diagnosis and therapy of cancer. A potential drawback of a number of reported radiopeptides is the rapid washout of a substantial fraction of the initially delivered radioactivity from cancer cells and tumors. This renders the initial targeting effort in part futile and results in a lower imaging quality and efficacy of the radiotracer than achievable. We are investigating the combination of internalizing radiopeptides with molecular entities specific for an intracellular target. By enabling intracellular interactions of the radioconjugate, we aim at reducing/decelerating the externalization of radioactivity from cancer cells. Using the “click-to-chelate” approach, the 99mTc-tricarbonyl core as a reporter probe for single-photon emission computed tomography (SPECT) was combined with the binding sequence of bombesin for extracellular targeting of the gastrin-releasing peptide receptor (GRP-r) and peptidic inhibitors of the cytosolic heat shock 90 protein (Hsp90) for intracellular targeting. Receptor-specific uptake of the multifunctional radioconjugate could be confirmed, however, the cellular washout of radioactivity was not improved. We assume that either endosomal trapping or lysosomal degradation of the radioconjugate is accountable for these observations. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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286 KiB  
Article
Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals
by Matthias Kuntzsch, Denis Lamparter, Nils Brüggener, Marco Müller, Gabriele J. Kienzle and Gerald Reischl
Pharmaceuticals 2014, 7(5), 621-633; https://doi.org/10.3390/ph7050621 - 14 May 2014
Cited by 33 | Viewed by 10174
Abstract
Kryptofix® 2.2.2 (Kry) or tetrabutylammonium (TBA) are commonly used as phase transfer catalysts in 18F-radiopharmaceutical productions for positron emission tomography (PET). Due to their toxicity, quality control has to be performed before administration of the tracer to assure that limit concentration [...] Read more.
Kryptofix® 2.2.2 (Kry) or tetrabutylammonium (TBA) are commonly used as phase transfer catalysts in 18F-radiopharmaceutical productions for positron emission tomography (PET). Due to their toxicity, quality control has to be performed before administration of the tracer to assure that limit concentration of residual reagent is not reached. Here, we describe the successful development and pharmaceutical validation (for specificity, accuracy and detection limit) of a simplified color spot test on TLC plates. We were able to prove its applicability as a general, time and resources saving, easy to handle and reliable method in daily routine analyzing 18F-tracer formulations for Kry (in [18F]FDG or [18F]FECh) or TBA contaminations (in [18F]FLT) with special regard to complex matrix compositions. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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353 KiB  
Article
Synthesis, Radiolabelling and In Vitro Characterization of the Gallium-68-, Yttrium-90- and Lutetium-177-Labelled PSMA Ligand, CHX-A''-DTPA-DUPA-Pep
by Benjamin Baur, Christoph Solbach, Elena Andreolli, Gordon Winter, Hans-Jürgen Machulla and Sven N. Reske
Pharmaceuticals 2014, 7(5), 517-529; https://doi.org/10.3390/ph7050517 - 29 Apr 2014
Cited by 37 | Viewed by 12778
Abstract
Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy [...] Read more.
Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively) and resulted in nearly quantitative radiochemical yields within 5 min. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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702 KiB  
Article
In Vivo Monitoring of the Antiangiogenic Effect of Neurotensin Receptor-Mediated Radiotherapy by Small-Animal Positron Emission Tomography: A Pilot Study
by Simone Maschauer, Tina Ruckdeschel, Philipp Tripal, Roland Haubner, Jürgen Einsiedel, Harald Hübner, Peter Gmeiner, Torsten Kuwert and Olaf Prante
Pharmaceuticals 2014, 7(4), 464-481; https://doi.org/10.3390/ph7040464 - 16 Apr 2014
Cited by 18 | Viewed by 9194
Abstract
The neurotensin receptor (NTS1) has emerged as an interesting target for molecular imaging and radiotherapy of NTS-positive tumors due to the overexpression in a range of tumors. The aim of this study was to develop a 177Lu-labeled NTS1 radioligand, its application for [...] Read more.
The neurotensin receptor (NTS1) has emerged as an interesting target for molecular imaging and radiotherapy of NTS-positive tumors due to the overexpression in a range of tumors. The aim of this study was to develop a 177Lu-labeled NTS1 radioligand, its application for radiotherapy in a preclinical model and the imaging of therapy success by small-animal positron emission tomography (µPET) using [68Ga]DOTA-RGD as a specific tracer for imaging angiogenesis. The 177Lu-labeled peptide was subjected to studies on HT29-tumor-bearing nude mice in vivo, defining four groups of animals (single dose, two fractionated doses, four fractionated doses and sham-treated animals). Body weight and tumor diameters were determined three times per week. Up to day 28 after treatment, µPET studies were performed with [68Ga]DOTA-RGD. At days 7–10 after treatment with four fractionated doses of 11–14 MBq (each at days 0, 3, 6 and 10), the tumor growth was slightly decreased in comparison with untreated animals. Using a single high dose of 51 MBq, a significantly decreased tumor diameter of about 50% was observed with the beginning of treatment. Our preliminary PET imaging data suggested decreased tumor uptake values of [68Ga]DOTA-RGD in treated animals compared to controls at day 7 after treatment. This pilot study suggests that early PET imaging with [68Ga]DOTA-RGD in radiotherapy studies to monitor integrin expression could be a promising tool to predict therapy success in vivo. Further successive PET experiments are needed to confirm the significance and predictive value of RGD-PET for NTS-mediated radiotherapy. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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532 KiB  
Article
Folate Receptor Targeted Alpha-Therapy Using Terbium-149
by Cristina Müller, Josefine Reber, Stephanie Haller, Holger Dorrer, Ulli Köster, Karl Johnston, Konstantin Zhernosekov, Andreas Türler and Roger Schibli
Pharmaceuticals 2014, 7(3), 353-365; https://doi.org/10.3390/ph7030353 - 13 Mar 2014
Cited by 70 | Viewed by 9487
Abstract
Terbium-149 is among the most interesting therapeutic nuclides for medical applications. It decays by emission of short-range α-particles (Eα = 3.967 MeV) with a half-life of 4.12 h. The goal of this study was to investigate the anticancer efficacy of a 149 [...] Read more.
Terbium-149 is among the most interesting therapeutic nuclides for medical applications. It decays by emission of short-range α-particles (Eα = 3.967 MeV) with a half-life of 4.12 h. The goal of this study was to investigate the anticancer efficacy of a 149Tb-labeled DOTA-folate conjugate (cm09) using folate receptor (FR)-positive cancer cells in vitro and in tumor-bearing mice. 149Tb was produced at the ISOLDE facility at CERN. Radiolabeling of cm09 with purified 149Tb resulted in a specific activity of ~1.2 MBq/nmol. In vitro assays performed with 149Tb-cm09 revealed a reduced KB cell viability in a FR-specific and activity concentration-dependent manner. Tumor-bearing mice were injected with saline only (group A) or with 149Tb-cm09 (group B: 2.2 MBq; group C: 3.0 MBq). A significant tumor growth delay was found in treated animals resulting in an increased average survival time of mice which received 149Tb-cm09 (B: 30.5 d; C: 43 d) compared to untreated controls (A: 21 d). Analysis of blood parameters revealed no signs of acute toxicity to the kidneys or liver in treated mice over the time of investigation. These results demonstrated the potential of folate-based α-radionuclide therapy in tumor-bearing mice. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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868 KiB  
Article
Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor
by Linjing Mu, Roger Slavik, Adrienne Müller, Kasim Popaj, Stjepko Čermak, Markus Weber, Roger Schibli, Stefanie D. Krämer and Simon M. Ametamey
Pharmaceuticals 2014, 7(3), 339-352; https://doi.org/10.3390/ph7030339 - 6 Mar 2014
Cited by 17 | Viewed by 7788
Abstract
Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a [...] Read more.
Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%–25% radiochemical yield (decay corrected) and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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2299 KiB  
Article
Asymmetric Synthesis of Spirocyclic 2-Benzopyrans for Positron Emission Tomography of σ1 Receptors in the Brain
by Katharina Holl, Dirk Schepmann, Steffen Fischer, Friedrich-Alexander Ludwig, Achim Hiller, Cornelius K. Donat, Winnie Deuther-Conrad, Peter Brust and Bernhard Wünsch
Pharmaceuticals 2014, 7(1), 78-112; https://doi.org/10.3390/ph7010078 - 22 Jan 2014
Cited by 2 | Viewed by 8326
Abstract
Sharpless asymmetric dihydroxylation of styrene derivative 6 afforded chiral triols (R)-7 and (S)-7, which were cyclized with tosyl chloride in the presence of Bu2SnO to provide 2-benzopyrans (R)-4 and (S)-4 with high [...] Read more.
Sharpless asymmetric dihydroxylation of styrene derivative 6 afforded chiral triols (R)-7 and (S)-7, which were cyclized with tosyl chloride in the presence of Bu2SnO to provide 2-benzopyrans (R)-4 and (S)-4 with high regioselectivity. The additional hydroxy moiety in the 4-position was exploited for the introduction of various substituents. Williamson ether synthesis and replacement of the Boc protective group with a benzyl moiety led to potent σ1 ligands with high σ1/σ2-selectivity. With exception of the ethoxy derivative 16, the (R)-configured enantiomers represent eutomers with eudismic ratios of up to 29 for the ester (R)-18. The methyl ether (R)-15 represents the most potent σ1 ligand of this series of compounds, with a Ki value of 1.2 nM and an eudismic ratio of 7. Tosylate (R)-21 was used as precursor for the radiosynthesis of [18F]-(R)-20, which was available by nucleophilic substitution with K[18F]F K222 carbonate complex. The radiochemical yield of [18F]-(R)-20 was 18%–20%, the radiochemical purity greater than 97% and the specific radioactivity 175–300 GBq/µmol. Although radiometabolites were detected in plasma, urine and liver samples, radiometabolites were not found in brain samples. After 30 min, the uptake of the radiotracer in the brain was 3.4% of injected dose per gram of tissue and could be reduced by coadministration of the σ1 antagonist haloperidol. [18F]-(R)-20 was able to label those regions of the brain, which were reported to have high density of σ1 receptors. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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Review

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1366 KiB  
Review
Imaging Biomarkers or Biomarker Imaging?
by Markus Mitterhauser and Wolfgang Wadsak
Pharmaceuticals 2014, 7(7), 765-778; https://doi.org/10.3390/ph7070765 - 25 Jun 2014
Cited by 12 | Viewed by 7445
Abstract
Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI)” in that context. Molecular probes (MPs) comprise all kinds of [...] Read more.
Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI)” in that context. Molecular probes (MPs) comprise all kinds of molecules administered to an organism which inherently carry a signalling moiety. This review highlights the basic concepts and differences of molecular probe imaging using specific biomarkers. In particular, PET radiopharmaceuticals are discussed in more detail. Specific radiochemical and radiopharmacological aspects as well as some legal issues are presented. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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1227 KiB  
Review
Radiolabeling of Nanoparticles and Polymers for PET Imaging
by Katharina Stockhofe, Johannes M. Postema, Hanno Schieferstein and Tobias L. Ross
Pharmaceuticals 2014, 7(4), 392-418; https://doi.org/10.3390/ph7040392 - 2 Apr 2014
Cited by 103 | Viewed by 17027
Abstract
Nanomedicine has become an emerging field in imaging and therapy of malignancies. Nanodimensional drug delivery systems have already been used in the clinic, as carriers for sensitive chemotherapeutics or highly toxic substances. In addition, those nanodimensional structures are further able to carry and [...] Read more.
Nanomedicine has become an emerging field in imaging and therapy of malignancies. Nanodimensional drug delivery systems have already been used in the clinic, as carriers for sensitive chemotherapeutics or highly toxic substances. In addition, those nanodimensional structures are further able to carry and deliver radionuclides. In the development process, non-invasive imaging by means of positron emission tomography (PET) represents an ideal tool for investigations of pharmacological profiles and to find the optimal nanodimensional architecture of the aimed-at drug delivery system. Furthermore, in a personalized therapy approach, molecular imaging modalities are essential for patient screening/selection and monitoring. Hence, labeling methods for potential drug delivery systems are an indispensable need to provide the radiolabeled analog. In this review, we describe and discuss various approaches and methods for the labeling of potential drug delivery systems using positron emitters. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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Graphical abstract

211 KiB  
Review
Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy
by Wiebke Sihver, Jens Pietzsch, Mechthild Krause, Michael Baumann, Jörg Steinbach and Hans-Jürgen Pietzsch
Pharmaceuticals 2014, 7(3), 311-338; https://doi.org/10.3390/ph7030311 - 5 Mar 2014
Cited by 59 | Viewed by 11332
Abstract
The epidermal growth factor receptor (EGFR) has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a) chemotherapy for treatment of colorectal [...] Read more.
The epidermal growth factor receptor (EGFR) has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a) chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b) with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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