Article
Immunology
Matthew F. L. Parker, Marina Lopez-Alvarez, Aryn A. Alanizi, Justin M. Luu, Ilona Polvoy, Alexandre M. Sorlin, Hecong Qin, Sanghee Lee, Sarah J. Rabbitt, Priamo A. Pichardo-Gonzalez, Alvaro A. Ordonez, Joseph Blecha, Oren S. Rosenberg, Robert R. Flavell, Joanne Engel, Sanjay K. Jain, Michael A. Ohliger, David M. Wilson
Summary: The study compared the performance of PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were evaluated for their ability to distinguish Staphylococcus aureus, the most common non-tuberculous pathogen in VDO, from Escherichia coli.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Engineering, Biomedical
Eloise Thomas, Clelia Mathieu, Patricia Moreno-Gaona, Vincent Mittelheisser, Francois Lux, Olivier Tillement, Xavier Pivot, Paiman Peter Ghoroghchian, Alexandre Detappe
Summary: A novel PET-based anti-BCMA nanoplatform labeled with Cu-64 has shown improved sensitivity and specificity in monitoring minute plasma cell populations in the spine and femur compared to traditional immunoPET approaches in detecting tumor cells in MM patients. This immuno-nanoPET platform has the potential to enhance the management of MM patients when combined with tumor biopsy.
ADVANCED HEALTHCARE MATERIALS
(2022)
Review
Biochemistry & Molecular Biology
Michael R. Kilbourn
Summary: The application of positron emission tomography (PET) imaging to study brain biochemistry, especially dopamine neurotransmission, has significantly grown over the past 40 years. PET imaging of dopaminergic functions in the central nervous system is routinely used for research in neurology, psychiatry, drug abuse and addiction, as well as drug development. The key advancement in PET imaging is the development of unique radiotracers labeled with positron-emitting radionuclides like carbon-11 and fluorine-18, which have greatly contributed to the progress in this field.
Article
Pharmacology & Pharmacy
Jindian Li, Juno Van Valkenburgh, Jianyang Fang, Deliang Zhang, Yingxi Chen, Quan Chen, Guorong Jia, Austin Z. Chen, Xianzhong Zhang, Kai Chen
Summary: In this study, a novel radiofluorinated riboflavin probe (18F-RFTA) was developed for specific and selective imaging of RFVT3-positive tumors. The probe demonstrated high radiochemical purity, binding affinity to RFVT3, and stability in vitro and in vivo. PET imaging showed significantly higher uptake of 18F-RFTA in RFVT3-expressing tumors compared to muscle.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Santosh R. Alluri, Yusuke Higashi, Kun-Eek Kil
Summary: Chemokines and their receptors play crucial roles in maintaining the physiological functions of various cells, especially immune cells. They guide leukocytes to respond to inflammatory reactions and infectious agents, as well as support the differentiation, proliferation, and metastasis of tumor cells. Advances in the development of radiotracers for chemokine receptors have shed new light on cancer and cardiovascular research and drug development.
Review
Biochemistry & Molecular Biology
Lucas Beroske, Tim Van den Wyngaert, Sigrid Stroobants, Pieter Van der Veken, Filipe Elvas
Summary: Molecular imaging of apoptosis using activated Caspase-3 as a target provides important methods for diagnosis and monitoring of diseases. Challenges in designing Caspase-3 radiotracers include selectivity, cell permeability, and transient activation. Nuclear imaging, with its high tissue penetration depth and sensitivity, is a good option for detecting small changes in apoptosis levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Multidisciplinary
Arno Christiaan Gouws, Hendrik Gerhardus Kruger, Olivier Gheysens, Jan Rijn Zeevaart, Thavendran Govender, Tricia Naicker, Thomas Ebenhan
Summary: The excellent features of non-invasive molecular imaging, coupled with the progressive technology and global impact of PET scanners, provide encouraging prospects for investigating new concepts in the clinical care of complex infectious diseases. This article reviews and critically evaluates the development efforts of antibiotic-derived PET radiopharmaceuticals for infection imaging.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Pharmacology & Pharmacy
Lingling Zhang, Kuan Hu, Tuo Shao, Lu Hou, Shaojuan Zhang, Weijian Ye, Lee Josephson, Jeffrey H. Meyer, Ming-Rong Zhang, Neil Vasdev, Jinghao Wang, Hao Xu, Lu Wang, Steven H. Liang
Summary: The 18 kDa translocator protein (TSPO) plays a key role in neuroinflammation and several TSPO-targeted PET tracers have been developed, some of which have advanced to clinical research studies.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Radiology, Nuclear Medicine & Medical Imaging
Weili Ma, Jiwei Mao, Jianfeng Yang, Ting Wang, Zhen Hua Zhao
Summary: This study systematically assessed the early detection rate of biochemical prostate cancer recurrence using choline, fluciclovine, and PSMA. The results showed that the detection rates of PSMA-radiotracers were greater than those of choline-radiotracers and fluciclovine-radiotracers at the patient level, especially with F-18-labeled PSMA.
EUROPEAN RADIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Brian J. Lopresti, Sarah K. Royse, Chester A. Mathis, Savannah A. Tollefson, Rajesh Narendran
Summary: With the emergence of PET, psychiatry gained access to a non-invasive tool for assessing human brain function. Early applications focused on measuring blood flow and metabolism, but specific probes for dopamine and serotonin receptors were later developed. However, the development of monoamine-enhancing drugs was not very successful, leading to a shift in drug development towards other targets. In recent years, PET imaging techniques have also been developed for studying non-monoamine targets.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Neurosciences
Lieneke Katharina Janssen, Annette Horstmann
Summary: Dopamine plays a crucial role in adaptive behavior, with obesity-related alterations affecting the central dopamine system, as shown in molecular neuroimaging studies. While there are associations between obesity and substrates of the dopamine system in humans, it is unlikely that obesity can be traced back to a single dopaminergic cause.
Article
Pharmacology & Pharmacy
Ahmed Haider, Xiaoyun Deng, Olivia Mastromihalis, Stefanie K. Pfister, Troels E. Jeppesen, Zhiwei Xiao, Vi Pham, Shaofa Sun, Jian Rong, Chunyu Zhao, Jiahui Chen, Yinlong Li, Theresa R. Connors, April T. Davenport, James B. Daunais, Vahid Hosseini, Wenqing Ran, Arthur Christopoulos, Lu Wang, Celine Valant, Steven H. Liang
Summary: This study aimed to develop a suitable M4 PET ligand for the non-invasive visualization of M4 in the brain. The compound 12 was identified as a subtype-selective positive allosteric modulator (PAM) and its radiofluorinated analogue showed moderate specificity in rodent brain sections. However, in non-human primates and humans, the presence of carbachol did not improve the specificity and selectivity of the radioligand.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Chemistry, Medicinal
M. Yu. Yushin, A. G. Tyrkov, A. V. Lutsenko, L. V. Saroyants, G. N. Genatullina, A. K. Ayupova
Summary: The effect of 5-aryl(hetaryl)methylidene-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-triones and 5-(2-chloropropylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-triones on the viability of M. tuberculosis H(37)Rv strain was investigated. Minimum inhibitory and bactericidal concentrations, as well as acute toxicity in mice, were determined. Compounds XIII, XIV, XVII, and XIX exhibited the strongest antituberculotic activity against M. tuberculosis H(37)Rv, suggesting their potential for further development as effective antituberculotic drugs.
PHARMACEUTICAL CHEMISTRY JOURNAL
(2023)
Review
Chemistry, Medicinal
Valeria Burianova, Stanislav Kalinin, Claudiu T. Supuran, Mikhail Krasavin
Summary: The review provides a comprehensive summary of the progress achieved in developing PET tracers based on CA IX and XII, including monoclonal antibodies, biomolecules, and small-molecule ligands.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Catherine G. Fitzgerald Dickmann, Alexander F. F. McDonald, Nhi Huynh, Angela Rigopoulos, Zhanqi Liu, Nancy Guo, Laura D. D. Osellame, Michael A. A. Gorman, Michael W. W. Parker, Hui K. K. Gan, Andrew M. M. Scott, Uwe Ackermann, Ingrid J. G. Burvenich, Jonathan M. M. White
Summary: A novel molecule, [F-18]BiPET-2, radiolabelled with positron emitting fluorine-18, has been developed and evaluated in vitro and preclinically in glioblastoma models.
CHEMICAL COMMUNICATIONS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Wolfgang P. Fendler, Matthias Eiber, Mohsen Beheshti, Jamshed Bomanji, Jeremie Calais, Francesco Ceci, Steve Y. Cho, Stefano Fanti, Frederik L. Giesel, Karolien Goffin, Uwe Haberkorn, Heather Jacene, Phillip J. Koo, Klaus Kopka, Bernd J. Krause, Liza Lindenberg, Charles Marcus, Felix M. Mottaghy, Daniela E. Oprea-Lager, Joseph R. Osborne, Morand Piert, Steven P. Rowe, Heiko Schoeder, Simon Wan, Hans-Jurgen Wester, Thomas A. Hope, Ken Herrmann
Summary: This article aims to provide updated guidance and standards for the use of PSMA PET/CT in imaging prostate cancer. It discusses procedures and characteristics of various PSMA small radioligands and different clinical scenarios for their use. The document is intended to support clinicians and technicians in implementing PSMA PET/CT imaging in both research and routine practice.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Chemistry, Medicinal
Florian Brandt, Martin Ullrich, Johanna Wodtke, Klaus Kopka, Michael Bachmann, Reik Loeser, Jens Pietzsch, Hans-Juergen Pietzsch, Robert Wodtke
Summary: The use of radioligands for targeted endoradionuclide therapy is limited due to their toxicity to healthy tissues, specifically the kidneys. However, targeting enzymes in the renal brush border membrane using cleavable linkers that can form fast clearing radionuclide fragments is gaining interest. In this study, a library of 64Cu-labeled cleavable linkers was synthesized and their substrate potentials towards neprilysin (NEP) were quantified, leading to the establishment of structure-activity relationships. It was found that a substrate-based targeting of NEP in the kidneys with small peptides resulted in premature cleavage in the bloodstream, highlighting the importance of additional targeting of albumin for kidney-specific NEP targeting.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ali Afshar-Oromieh, Matthias Eiber, Wolfgang Fendler, Matthias Schmidt, Kambiz Rahbar, Hojjat Ahmadzadehfar, Lale Umutlu, Boris Hadaschik, Oliver W. Hakenberg, Paolo Fornara, Jens Kurth, O. Neels, Hans-Juergen Wester, Markus Schwaiger, Klaus Kopka, Uwe Haberkorn, Ken Herrmann, Bernd J. Krause
Summary: PSMA-PET/CT has been widely used for imaging prostate cancer globally, especially for recurrent prostate cancer. Promising results have been obtained for primary staging of high-risk prostate cancer. Multiple PSMA-ligands are available for clinical use, but only (68) Ga-PSMA-11 and (18) F-DCFPyL have official approval. Late imaging can help clarify unclear findings as the contrast in PSMA-PET/CT increases with time. PSMA-PET/CT should be performed before starting androgen deprivation therapy (ADT) due to reduced visibility of PC lesions with (long term) ADT. Hydration and forced diuresis are recommended for PSMA-ligands excreted primarily via the kidneys to increase visibility of tumor lesions adjacent to the urinary bladder. PSMA-ligands are taken up in multiple normal organs and can show unspecific focal bone uptake with certain (18) F-labeled PSMA-ligands. PSMA is expressed in the neovasculature of practically all solid tumors, although usually to a lesser extent than in PC. Multiple benign lesions and inflammatory processes also take up PSMA-ligands, usually to a lesser extent than PC.
NUKLEARMEDIZIN-NUCLEAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Martin Ullrich, Susan Richter, Josephine Liers, Stephan Drukewitz, Markus Friedemann, Joerg Kotzerke, Christian G. Ziegler, Svenja Noelting, Klaus Kopka, Jens Pietzsch
Summary: This study evaluates the effects of epigenetic drugs on SSTR2 levels and sensitivity to [177Lu]Lu-DOTA-TATE in mouse pheochromocytoma models, and found that epigenetic drugs have a therapeutic benefit, although the exact mechanism is unknown.
Article
Radiology, Nuclear Medicine & Medical Imaging
Clemens Kratochwil, Wolfgang P. Fendler, Matthias Eiber, Michael S. Hofman, Louise Emmett, Jeremie Calais, Joseph R. Osborne, Amir Iravani, Phillip Koo, Liza Lindenberg, Richard P. Baum, Murat Fani Bozkurt, Roberto Delgado C. Bolton, Samer Ezziddin, Flavio Forrer, Rodney J. Hicks, Thomas A. Hope, Levent Kabasakal, Mark Konijnenberg, Klaus Kopka, Michael Lassmann, Felix M. Mottaghy, Wim J. G. Oyen, Kambiz Rahbar, Heiko Schoder, Irene Virgolini, Lisa Bodei, Stefano Fanti, Uwe Haberkorn, Ken Hermann
Summary: PSMA is expressed in most clinically significant prostate adenocarcinomas, and PSMA PET imaging can easily identify patients with target-positive disease. Early-phase studies have shown promising results with PSMA-targeted radiopharmaceutical therapy using different targeting molecules and radiolabels. [Lu-177]Lu-PSMA-617 in combination with standard-of-care has been demonstrated to be safe and effective in patients with metastatic castration-resistant prostate cancer. Ongoing phase 3 trials are evaluating the radiopharmaceuticals [Lu-177]Lu-PSMA-617 and [Lu-177]Lu-PSMA-I&T.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Chemistry, Medicinal
Lea Ueberham, Daniel Guendel, Martin Kellert, Winnie Deuther-Conrad, Friedrich-Alexander Ludwig, Peter Loennecke, Aleksandr Kazimir, Klaus Kopka, Peter Brust, Rares-Petru Moldovan, Evamarie Hey-Hawkins
Summary: The synthesis and characterization of carborane-based 1,8-naphthyridinones and thiazoles as novel CB2R ligands was reported in this study. These compounds showed low nanomolar CB2R affinity, with LUZ5 exhibiting the highest affinity. An automated radiosynthesizer was used to obtain [18F]LUZ5-d8 with high radiochemical yield and purity. In vivo evaluation demonstrated the improved metabolic stability of [18F]LUZ5-d8 compared to [18F]JHU94620, and PET experiments in rats showed high uptake in spleen and low uptake in brain. The introduction of a carborane moiety is a useful strategy for modifying CB2R ligands and developing high-affinity CB2R ligands.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Lydia Behring, Gloria Ruiz-Gomez, Christian Trapp, Maryann Morales, Robert Wodtke, Martin Koeckerling, Klaus Kopka, M. Teresa Pisabarro, Jens Pietzsch, Reik Loeser
Summary: The potential of designing irreversible alkyne-based inhibitors of cysteine cathepsins was explored by isoelectronic replacement in reversibly acting potent peptide nitriles. The synthesis of dipeptide alkynes and analogous nitriles was developed and investigated for their inhibition of cathepsins B, L, S, and K. Extensive structure-activity relationships were derived, and the selectivity profiles of alkynes do not necessarily reflect those of the nitriles. The inhibitory activity at the cellular level was demonstrated for selected compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Fabian Krutzek, Cornelius K. K. Donat, Martin Ullrich, Kristof Zarschler, Marie-Charlotte Ludik, Anja Feldmann, Liliana R. R. Loureiro, Klaus Kopka, Sven Stadlbauer
Summary: PD-L1 plays a crucial role in immune responses against cancer. Nine small-molecule PD-L1 radiotracers with strong binding affinity have been synthesized, laying a promising foundation for the further development of PD-L1 small molecule PET radiotracers.
Article
Chemistry, Medicinal
Santiago Andres Bruehlmann, Martin Walther, Martin Kreller, Falco Reissig, Hans-Juergen Pietzsch, Torsten Kniess, Klaus Kopka
Summary: Theranostic matched pairs of radionuclides, including copper isotopes Cu-61, Cu-64, and Cu-67, have gained attention for their potential in diagnostic and therapeutic applications. Cu-67, in particular, plays a crucial role in future radiopharmaceutical development. This study focuses on producing high-purity Cu-67 using a 30MeV compact cyclotron and the Zn-70(p,alpha)Cu-67 reaction. Proton irradiation of Zn-70 targets and solid-phase extraction were used to achieve radionuclidic purities over 99.5% and apparent molar activities of up to 80MBq/nmol.
Article
Chemistry, Medicinal
Carsten Sven Kramer, Thines Kanagasundaram, Jessica Matthias, Klaus Kopka
Summary: Tracers for bimodal optical imaging and positron emission tomography combine various advantages into one molecule. These tracers can be used for tumor-specific visualization in PET/CT or PET/MRI, as well as intraoperative fluorescence-guided surgery and histological assessments. The introduction of a fluorinated silicon pyronine allows for PET activation and successful radiochemical conversion. Additionally, a library of red-shifted silicon rhodamines with different functionalizations was synthesized and their optical properties were characterized.
Article
Chemistry, Medicinal
Torsten Kniess, Joerg Zessin, Peter Maeding, Manuela Kuchar, Oliver Kiss, Klaus Kopka
Summary: This paper provides an overview of the radiosynthesis methods for [F-18]FMISO published so far. It discusses different precursors, radiolabeling approaches, purification methods, and automated radiosynthesizers used. The authors also report a GMP compliant radiosynthesis using original cassettes and an easy and efficient radiosynthesis using in-house prepared FASTlab cassettes.
EJNMMI RADIOPHARMACY AND CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Reik Loeser, Manuela Kuchar, Robert Wodtke, Christin Neuber, Birgit Belter, Klaus Kopka, Lakshmi Santhanam, Jens Pietzsch
Summary: The understanding of the contribution of the tumour microenvironment to cancer progression and metastasis, in particular the interplay between tumour cells, fibroblasts and the extracellular matrix has grown tremendously over the last years. Lysyl oxidases are increasingly recognised as key players in this context, in addition to their function as drivers of fibrotic diseases.
Article
Chemistry, Multidisciplinary
Barbara Wenzel, Maximilian Schmid, Rodrigo Teodoro, Rares-Petru Moldovan, Thu Hang Lai, Franziska Mitrach, Klaus Kopka, Bjoern Fischer, Michaela Schulz-Siegmund, Peter Brust, Michael C. Hacker
Summary: This study presents the synthesis, radiofluorination, and purification process of an anionic amphiphilic teroligomer, which serves as a stabilizer for siRNA-loaded calcium phosphate nanoparticles (CaP-NPs). The F-18-labeled polymer enables the tracking of the distribution of CaP-NPs in brain tumors through positron emission tomography. The synthesis involved the production of an unmodified teroligomer and subsequent derivatization, followed by F-18-labeling using copper-catalyzed cycloaddition. Purification was achieved through solid-phase extraction and size-exclusion chromatography.
Article
Chemistry, Inorganic & Nuclear
Marlene Schlesinger, Christian Jentschel, Hans-Juergen Pietzsch, Klaus Kopka, Constantin Mamat
Summary: Click chemistry, especially copper-free click reactions, has gained significant attention in the field of radiopharmaceutical sciences for radiolabelling purposes. This study investigated a new chelator for strain-promoted cycloaddition (SPAAC) without the need for copper, and compared it with a conventional chelator for radiolabelling. The results showed that the new chelator, containing the 2,2'-dipicolylamine (DPA) moiety, was successful in radiolabelling under mild conditions.
DALTON TRANSACTIONS
(2023)
Meeting Abstract
Radiology, Nuclear Medicine & Medical Imaging
Constantin Mamat, Marlene Schlesinger, Christian Jentschel, Hans-Jurgen Pietzsch, Klaus Kopka
NUCLEAR MEDICINE AND BIOLOGY
(2022)