Review
Chemistry, Multidisciplinary
Ya-Qiong Yan, Hao Wang, Yuliang Zhao
Summary: Radionuclide imaging is a premier imaging method in clinical practice, utilizing PET and SPECT to detect anatomical abnormalities. Peptides as targeting vectors for contrast agents offer high specificity and low toxicity. Radiolabeled peptide probes have become essential tools for clinical radionuclide diagnosis.
CHINESE CHEMICAL LETTERS
(2022)
Review
Radiology, Nuclear Medicine & Medical Imaging
Xiyi Qin, Han Jiang, Yu Liu, Hong Zhang, Mei Tian
Summary: Apoptosis is a natural, non-inflammatory form of programmed cell death that can be detected through characteristic biochemical changes. Imaging with radionuclide tracers allows for selective detection of apoptotic cell death in vivo, potentially serving as diagnostic markers, early-response indicators, and prognostic predictors.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Oncology
Steven P. Rowe, Martin G. Pomper
Summary: Molecular imaging, defined as visualizing, characterizing, and measuring biological processes at the molecular and cellular levels, has rapidly developed in recent years, with a particular focus on oncology for early detection and optimal disease management. The expansion of molecular imaging is driven by new animal models, sensitive imaging devices, high-throughput methods, genetic manipulation techniques, and cloud computing. Researchers and clinicians are utilizing molecular imaging for a variety of physiological processes, with a focus on oncology for its potential in detecting diseases at an early stage.
CA-A CANCER JOURNAL FOR CLINICIANS
(2022)
Review
Oncology
Huiling Li, Zhen Liu, Lujie Yuan, Kevin Fan, Yongxue Zhang, Weibo Cai, Xiaoli Lan
Summary: Breast cancer is a common malignant tumor that affects women globally, posing a significant threat to their health. Early detection of breast cancer can greatly improve patient prognosis and survival rates, with radionuclide molecular imaging techniques offering advantages in functional detection. Using radionuclide-labeled compounds for noninvasive visualization of biological processes helps elucidate the metabolic state of breast cancer, while receptor-targeted radionuclide molecular imaging is sensitive and specific for visualizing overexpressed molecular markers in the disease, aiding in early diagnosis and improved patient care. Rapid developments in radionuclide probes are contributing to the diagnosis of breast cancer across various aspects, with promising tools being developed for early detection.
Review
Biochemistry & Molecular Biology
Loredana G. G. Marcu, Leyla Moghaddasi, Eva Bezak
Summary: Cancer stem cells are crucial in tumor development, growth, and spread. Their unique properties make them resistant to treatment, often leading to therapy failure. Research into identifying, targeting, and eliminating these cells is believed to revolutionize oncology treatment. This review discusses state-of-the-art functional imaging techniques for identifying cancer stem cells through various pathways and mechanisms. It presents in vivo molecular techniques that are currently available or awaiting clinical implementation while highlighting challenges and future prospects for cancer stem cell imaging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Aleksi Kokkonen, Emma A. Honkanen, Daniel T. Corp, Juho Joutsa
Summary: Deep brain stimulation (DBS) is an effective treatment for various brain disorders, but its mechanisms of action and detailed molecular effects still need further investigation.
Article
Medicine, General & Internal
Mitchel R. Stacy
Summary: Peripheral arterial disease (PAD) is a non-coronary artery atherosclerotic disorder that affects the lower extremities and is associated with various health consequences. The diagnosis is typically made using non-invasive tests, but nuclear medicine techniques have recently emerged as a potential tool for assessing the functional consequences of PAD-related limb ischemia.
FRONTIERS IN MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Krystyna Pyrzynska, Krzysztof Kilian, Mateusz Pegier
Summary: This paper provides a brief overview of the application of porphyrin ligands in tumor diagnostics, including the chelation of metallic radioisotopes to form radiopharmaceuticals and the evaluation of metabolic changes in the human body through SPECT and PET. The chelation reactions are discussed in terms of the conditions, kinetics, and complex stability.
Article
Biochemistry & Molecular Biology
Winn Aung, Atsushi B. Tsuji, Aya Sugyo, Masayuki Fujinaga, Ming-Rong Zhang, Tatsuya Higashi
Summary: Photoimmunotherapy (PIT) combined with chemotherapy shows improved efficacy in cancer treatment. By evaluating the super-enhanced permeability and retention effect of different molecular weight drugs, promising candidates for combined PIT treatment were identified, leading to increased drug accumulation in tumors. Further preclinical and clinical studies are encouraged to develop combination therapy of PIT with conventional anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Medicinal
Shalini Sharma, Mukesh K. Pandey
Summary: This article highlights the significant progress made in molecular imaging and radionuclide therapy in the last two decades. It discusses advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy in terms of their production routes and ease of radiolabeling. The review also includes the use of astatine, a metalloid, in imaging and radionuclide therapy. Furthermore, it explores beta-minus and alpha-emitting radionuclides for therapy, focusing on their production routes, targeted radiopharmaceuticals, and current clinical translation stage.
Review
Biochemistry & Molecular Biology
Nicolas Nicastro, Umberto Nencha, Pierre R. Burkhard, Valentina Garibotto
Summary: This study summarizes the current evidence on dopaminergic molecular imaging in the diagnostic evaluation of Parkinson's disease (PD), atypical parkinsonian syndromes, and dementia with Lewy bodies (DLB), as well as its potential to distinguish these conditions and estimate disease progression. Dopamine imaging has an outstanding potential for early detection of neurodegeneration.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Xiaomeng Wang, Ying-Hwey Nai, Julian Gan, Cheryl Pei Ling Lian, Fraser Kirwan Ryan, Forest Su Lim Tan, Dexter Yak Seng Chan, Jun Jie Ng, Zhiwen Joseph Lo, Tze Tec Chong, Derek John Hausenloy
Summary: Peripheral artery disease (PAD) is a common and debilitating condition characterized by the narrowing of limb arteries. Non-invasive imaging techniques such as CT, MRI, and nuclear imaging have proven valuable in assessing PAD plaques and vessel walls. This review explores the advantages, limitations, and recent advancements of these imaging techniques, as well as the importance of molecular markers in PAD pathophysiology. Integrating molecular and imaging markers holds potential for improving our understanding of PAD, but technical constraints and the need for new molecular markers pose challenges.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Eric Xie, Eric Sung, Elie Saad, Natalia Trayanova, Katherine C. C. Wu, Jonathan Chrispin
Summary: Sudden cardiac death is a major cause of mortality, and conventional risk stratification methods based on ejection fraction may not be accurate for certain patients. Advanced cardiac imaging techniques such as CMR, SPECT, PET, and CT offer promising and non-invasive means of assessing the underlying myocardial substrate and predicting the risk of sudden death. Machine learning algorithms can enhance predictive performance in combination with established imaging techniques.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
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.
Review
Cardiac & Cardiovascular Systems
Mahesh K. Vidula, Paco E. Bravo
Summary: Infiltrative cardiomyopathies are diseases that result from specific substances being deposited or abnormally stored in the heart, leading to impaired cardiac function and heart failure. Multimodality imaging is essential for the accurate non-invasive diagnosis of infiltrative cardiomyopathies, which is crucial for ensuring appropriate treatment and prognosis for patients.
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
Austin Craig, Florian Brandt, Jens Pietzsch, Klaus Kopka, Sven Stadlbauer, Markus Laube
NUCLEAR MEDICINE AND BIOLOGY
(2022)