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Article: 18

Waldmann, Christopher M / Kopka, Klaus / Wagner, Stefan

Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer

2020 Volume 216, Page(s) 283–318

Abstract: Noninvasive molecular imaging of cancer by means of the scintigraphic imaging modalities PET, PET/CT, and PET/MRI represents a powerful diagnostic tool in modern nuclear medicine. Radiotracers labeled with the prominent positron emitter fluorine-18 are ... ...

Abstract	Noninvasive molecular imaging of cancer by means of the scintigraphic imaging modalities PET, PET/CT, and PET/MRI represents a powerful diagnostic tool in modern nuclear medicine. Radiotracers labeled with the prominent positron emitter fluorine-18 are routinely used to target and visualize discrete biological structures dysregulated in the progression of cancer. Such tracers are therefore capable of detecting oncological pathologies in vivo at the cellular and subcellular level in a timely manner and are thereby used for early detection of cancer as well as monitoring for treatment response. This chapter describes a variety of important
MeSH term(s)	Fluorine Radioisotopes ; Humans ; Neoplasms/diagnostic imaging ; Positron Emission Tomography Computed Tomography/methods ; Radiopharmaceuticals
Chemical Substances	Fluorine Radioisotopes ; Radiopharmaceuticals ; Fluorine-18 (GZ5I74KB8G)
Language	English
Publishing date	2020-06-27
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0080-0015
ISSN	0080-0015
DOI	10.1007/978-3-030-42618-7_8
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Article ; Online: The Search for an Alternative to [

Waldmann, Christopher M / Stuparu, Andreea D / van Dam, R Michael / Slavik, Roger

Theranostics

2019 Volume 9, Issue 5, Page(s) 1336–1347

Abstract: The trend to inform personalized molecular radiotherapy with molecular imaging diagnostics, a concept referred to as theranostics, has transformed the field of nuclear medicine in recent years. The development of theranostic pairs comprising somatostatin ...

Abstract	The trend to inform personalized molecular radiotherapy with molecular imaging diagnostics, a concept referred to as theranostics, has transformed the field of nuclear medicine in recent years. The development of theranostic pairs comprising somatostatin receptor (SSTR)-targeting nuclear imaging probes and therapeutic agents for the treatment of patients with neuroendocrine tumors (NETs) has been a driving force behind this development. With the Neuroendocrine Tumor Therapy (NETTER-1) phase 3 trial reporting encouraging results in the treatment of well-differentiated, metastatic midgut NETs, peptide radioligand therapy (RLT) with the
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Biomedical Research/trends ; Fluorine Radioisotopes/administration & dosage ; Hormones/administration & dosage ; Humans ; Molecular Imaging/methods ; Molecular Targeted Therapy/methods ; Neuroendocrine Tumors/diagnosis ; Neuroendocrine Tumors/therapy ; Prospective Studies ; Somatostatin/administration & dosage ; Somatostatin/analogs & derivatives ; Theranostic Nanomedicine/methods
Chemical Substances	Antineoplastic Agents ; Fluorine Radioisotopes ; Hormones ; Somatostatin (51110-01-1) ; Fluorine-18 (GZ5I74KB8G)
Language	English
Publishing date	2019-02-14
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.31806
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Article ; Online: An automated synthesizer for electrochemical

Waldmann, Christopher M / Lebedev, Artem / Allison, Nathaniel / Sadeghi, Saman

Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine

2017 Volume 127, Page(s) 245–252

Abstract: ... ...

Abstract	Electrochemical
Language	English
Publishing date	2017-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1142596-9
ISSN	1872-9800 ; 0883-2889 ; 0969-8043
ISSN (online)	1872-9800
ISSN	0883-2889 ; 0969-8043
DOI	10.1016/j.apradiso.2017.06.028
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Article: Image quality analysis of

Rosar, Florian / Buchholz, Hans-Georg / Michels, Sebastian / Hoffmann, Manuela A / Piel, Markus / Waldmann, Christopher M / Rösch, Frank / Reuss, Stefan / Schreckenberger, Mathias

EJNMMI physics

2020 Volume 7, Issue 1, Page(s) 16

Abstract: Background: 44: Results: Despite the presence of high-energy γ-rays in : Conclusion: Based on these findings, ...

Abstract	Background: 44 Results: Despite the presence of high-energy γ-rays in Conclusion: Based on these findings,
Language	English
Publishing date	2020-03-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2768912-8
ISSN	2197-7364
ISSN	2197-7364
DOI	10.1186/s40658-020-0286-3
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Article ; Online: Automation of a Positron-emission Tomography (PET) Radiotracer Synthesis Protocol for Clinical Production.

Schopf, Eric / Waldmann, Christopher M / Collins, Jeffrey / Drake, Christopher / Slavik, Roger / van Dam, R Michael

Journal of visualized experiments : JoVE

2018 , Issue 140

Abstract: The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological targets and processes. However, the increasing number of different tracers creates challenges for ... ...

Abstract	The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological targets and processes. However, the increasing number of different tracers creates challenges for their production at radiopharmacies. While historically it has been practical to dedicate a custom-configured radiosynthesizer and hot cell for the repeated production of each individual tracer, it is becoming necessary to change this workflow. Recent commercial radiosynthesizers based on disposable cassettes/kits for each tracer simplify the production of multiple tracers with one set of equipment by eliminating the need for custom tracer-specific modifications. Furthermore, some of these radiosynthesizers enable the operator to develop and optimize their own synthesis protocols in addition to purchasing commercially-available kits. In this protocol, we describe the general procedure for how the manual synthesis of a new PET tracer can be automated on one of these radiosynthesizers and validated for the production of clinical-grade tracers. As an example, we use the ELIXYS radiosynthesizer, a flexible cassette-based radiochemistry tool that can support both PET tracer development efforts, as well as routine clinical probe manufacturing on the same system, to produce [
MeSH term(s)	Automation ; Humans ; Positron-Emission Tomography/methods ; Radiochemistry ; Radiopharmaceuticals/chemical synthesis ; Software
Chemical Substances	Radiopharmaceuticals
Language	English
Publishing date	2018-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ISSN	1940-087X
ISSN (online)	1940-087X
DOI	10.3791/58428
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Article: Automation of a positron-emission tomography (pet) radiotracer synthesis protocol for clinical production

Schopf, Eric / Waldmann, Christopher M / Collins, Jeffrey / Drake, Christopher / Slavik, Roger / van Dam, R. Michael

Journal of visualized experiments. 2018 Oct. 26, , no. 140

2018

Abstract	The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological targets and processes. However, the increasing number of different tracers creates challenges for their production at radiopharmacies. While historically it has been practical to dedicate a custom-configured radiosynthesizer and hot cell for the repeated production of each individual tracer, it is becoming necessary to change this workflow. Recent commercial radiosynthesizers based on disposable cassettes/kits for each tracer simplify the production of multiple tracers with one set of equipment by eliminating the need for custom tracer-specific modifications. Furthermore, some of these radiosynthesizers enable the operator to develop and optimize their own synthesis protocols in addition to purchasing commercially-available kits. In this protocol, we describe the general procedure for how the manual synthesis of a new PET tracer can be automated on one of these radiosynthesizers and validated for the production of clinical-grade tracers. As an example, we use the ELIXYS radiosynthesizer, a flexible cassette-based radiochemistry tool that can support both PET tracer development efforts, as well as routine clinical probe manufacturing on the same system, to produce [18F]Clofarabine ([18F]CFA), a PET tracer to measure in vivo deoxycytidine kinase (dCK) enzyme activity. Translating a manual synthesis involves breaking down the synthetic protocol into basic radiochemistry processes that are then translated into intuitive chemistry "unit operations" supported by the synthesizer software. These operations can then rapidly be converted into an automated synthesis program by assembling them using the drag-and-drop interface. After basic testing, the synthesis and purification procedure may require optimization to achieve the desired yield and purity. Once the desired performance is achieved, a validation of the synthesis is carried out to determine its suitability for the production of the radiotracer for clinical use.
Keywords	automation ; chemistry ; computer software ; deoxycytidine ; enzyme activity ; equipment ; image analysis ; manufacturing ; pets ; phosphotransferases (kinases) ; positron-emission tomography ; purchasing ; tracer techniques
Language	English
Dates of publication	2018-1026
Size	p. e58428.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/58428
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Article ; Online: Heterogeneous cardiac sympathetic innervation gradients promote arrhythmogenesis in murine dilated cardiomyopathy.

Dajani, Al-Hassan J / Liu, Michael B / Olaopa, Michael A / Cao, Lucian / Valenzuela-Ripoll, Carla / Davis, Timothy J / Poston, Megan D / Smith, Elizabeth H / Contreras, Jaime / Pennino, Marissa / Waldmann, Christopher M / Hoover, Donald B / Lee, Jason T / Jay, Patrick Y / Javaheri, Ali / Slavik, Roger / Qu, Zhilin / Ajijola, Olujimi A

JCI insight

2023 Volume 8, Issue 22

Abstract: Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We ... ...

Abstract	Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve fibers versus controls. Further, the severity of transmural innervation gradients was correlated with VAs. Transmural innervation gradients were also identified in human left ventricular free wall samples from DCM versus controls. We investigated mechanisms underlying this relationship by in silico studies in 1D, 2D, and 3D models of failing and normal human hearts, finding that arrhythmogenesis increased as heterogeneity in sympathetic innervation worsened. Specifically, both DCM-induced myocyte electrical remodeling and spatially inhomogeneous innervation gradients synergistically worsened arrhythmogenesis. Thus, heterogeneous innervation gradients in DCM promoted arrhythmogenesis. Restoration of homogeneous sympathetic innervation in the failing heart may reduce VAs.
MeSH term(s)	Humans ; Mice ; Animals ; Cardiomyopathy, Dilated/diagnostic imaging ; Heart ; Myocardium ; Arrhythmias, Cardiac/diagnostic imaging ; Catecholamines
Chemical Substances	Catecholamines
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.157956
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Article ; Online: A Dual-Modality Linker Enables Site-Specific Conjugation of Antibody Fragments for

Zettlitz, Kirstin A / Waldmann, Christopher M / Tsai, Wen-Ting K / Tavaré, Richard / Collins, Jeffrey / Murphy, Jennifer M / Wu, Anna M

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2019 Volume 60, Issue 10, Page(s) 1467–1473

Abstract: Antibody-based dual-modality (PET/fluorescence) imaging enables both presurgery antigen-specific immuno-PET for noninvasive whole-body evaluation and intraoperative fluorescence for visualization of superficial tissue layers for image-guided surgery. ...

Abstract	Antibody-based dual-modality (PET/fluorescence) imaging enables both presurgery antigen-specific immuno-PET for noninvasive whole-body evaluation and intraoperative fluorescence for visualization of superficial tissue layers for image-guided surgery.
MeSH term(s)	Animals ; Antibodies/chemistry ; Antigens, Neoplasm/blood ; Carbocyanines/chemistry ; Cyclooctanes/chemistry ; Cysteine/chemistry ; Fluorescence ; Fluorescent Dyes ; Fluorine Radioisotopes/chemistry ; GPI-Linked Proteins/blood ; Humans ; Immunoglobulin Fragments ; Male ; Mice ; Microscopy, Fluorescence ; Neoplasm Proteins/blood ; Neoplasm Transplantation ; Optical Imaging ; Positron-Emission Tomography ; Prostatic Neoplasms/diagnostic imaging ; Radiopharmaceuticals ; Tissue Distribution
Chemical Substances	Antibodies ; Antigens, Neoplasm ; Carbocyanines ; Cyclooctanes ; Fluorescent Dyes ; Fluorine Radioisotopes ; GPI-Linked Proteins ; Immunoglobulin Fragments ; Neoplasm Proteins ; PSCA protein, human ; Radiopharmaceuticals ; cyanine dye 5 ; Fluorine-18 (GZ5I74KB8G) ; Cysteine (K848JZ4886)
Language	English
Publishing date	2019-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.118.223560
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Article ; Online: An Automated Multidose Synthesis of the Potentiometric PET Probe 4-[

Waldmann, Christopher M / Gomez, Adrian / Marchis, Phillip / Bailey, Sean T / Momcilovic, Milica / Jones, Anthony E / Shackelford, David B / Sadeghi, Saman

Molecular imaging and biology

2017 Volume 20, Issue 2, Page(s) 205–212

Abstract: Purpose: The aim of this study was the automated synthesis of the mitochondrial membrane potential sensor 4-[: Procedures: A three-pot, four-step synthesis was implemented on the ELIXYS FLEX/CHEM radiosynthesizer (Sofie Biosciences) and optimized for ...

Abstract	Purpose: The aim of this study was the automated synthesis of the mitochondrial membrane potential sensor 4-[ Procedures: A three-pot, four-step synthesis was implemented on the ELIXYS FLEX/CHEM radiosynthesizer (Sofie Biosciences) and optimized for radiochemical yield (RCY), radiochemical purity (RCP) as well as chemical purity during several production runs (n = 24). The compound was purified by solid-phase extraction (SPE) with a Sep-Pak Plus Accell CM cartridge, thereby avoiding HPLC purification. Results: Under optimized conditions, AY of 1.4-2.2 GBq of [ Conclusions: In initial attempts, the probe was synthesized with RCY < 0.6 % when starting activities up to 44.6 GBq were used. Rapid radiolysis of the intermediate 4-[
MeSH term(s)	Automation ; Molecular Probes/chemical synthesis ; Molecular Probes/chemistry ; Organophosphorus Compounds/chemical synthesis ; Organophosphorus Compounds/chemistry ; Positron-Emission Tomography ; Potentiometry
Chemical Substances	18F-fluorobenzyl triphenyl phosphonium ; Molecular Probes ; Organophosphorus Compounds
Language	English
Publishing date	2017-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2079160-4
ISSN	1860-2002 ; 1536-1632
ISSN (online)	1860-2002
ISSN	1536-1632
DOI	10.1007/s11307-017-1119-1
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Article ; Online: Novel fluorine-18 labeled 5-(1-pyrrolidinylsulfonyl)-7-azaisatin derivatives as potential PET tracers for in vivo imaging of activated caspases in apoptosis.

Waldmann, Christopher M / Hermann, Sven / Faust, Andreas / Riemann, Burkhard / Schober, Otmar / Schäfers, Michael / Haufe, Günter / Kopka, Klaus

Bioorganic & medicinal chemistry

2015 Volume 23, Issue 17, Page(s) 5734–5739

Abstract: The programmed type I cell death, defined as apoptosis, is induced by complex regulated signaling pathways that trigger the intracellular activation of executioner caspases-3, -6 and -7. Once activated, these enzymes initiate cellular death through ... ...

Abstract	The programmed type I cell death, defined as apoptosis, is induced by complex regulated signaling pathways that trigger the intracellular activation of executioner caspases-3, -6 and -7. Once activated, these enzymes initiate cellular death through cleavage of proteins which are responsible for DNA repair, signaling and cell maintenance. Several radiofluorinated inhibitors of caspases-3 and -7, comprising a moderate lipophilic 5-(1-pyrrolidinylsulfonyl)isatin lead structure, are currently being investigated for imaging apoptosis in vivo by us and others. The purpose of this study was to increase the intrinsic hydrophilicity of the aforementioned lead structure to alter the pharmacokinetic behavior of the resulting caspase-3 and -7 targeted radiotracer. Therefore, fluorinated and non-fluorinated derivatives of 5-(1-pyrrolidinylsulfonyl)-7-azaisatin were synthesized and tested for their inhibitory properties against recombinant caspases-3 and -7. Fluorine-18 has been introduced by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of an alkyne precursor with 2-[(18)F]fluoroethylazide. Using dynamic micro-PET biodistribution studies in vivo the kinetic behavior of one promising PET-compatible 5-pyrrolidinylsulfonyl 7-azaisatin derivative has been compared to a previously described isatin based radiotracer.
MeSH term(s)	Apoptosis/physiology ; Aza Compounds/chemical synthesis ; Aza Compounds/chemistry ; Caspases/metabolism ; Click Chemistry ; Fluorine Radioisotopes/chemistry ; Humans ; Hydrophobic and Hydrophilic Interactions ; Isatin/analogs & derivatives ; Isatin/chemical synthesis ; Isotope Labeling ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/chemistry ; Structure-Activity Relationship
Chemical Substances	Aza Compounds ; Fluorine Radioisotopes ; Radiopharmaceuticals ; Isatin (82X95S7M06) ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2015-09-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2015.07.014
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