Optimization of labeling and metabolite analysis of copper-64-labeled azamacrocyclic chelators by radio-LC-MS

Boswell, C. Andrew; McQuade, Paul; Weisman, Gary R.; Wong, Edward H.; Anderson, Carolyn J.

doi:10.1016/j.nucmedbio.2004.09.004

Cited by 38 publications

(43 citation statements)

References 26 publications

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“…The biodistribution at 4 hr demonstrates nearly complete clearance from all major organs with a %ID/g of < 0.80 (Figure 5) suggesting no transchelation occurred to blood proteins nor was Cu release observed in contrast to Cu-TETA complexes 7,8. Interestingly, no significant level of bone accumulation of 64 Cu-SB-TE1A1P was observed in the in vivo PET imaging study, in agreement with the biodistribution data (Figure 5).…”

Section: Resultssupporting

confidence: 82%

“…Despite its widespread use, TETA is not an optimal BFC for biomedical applications. Anderson and coworkers have demonstrated the dissociation of 64 Cu from TETA- d -Phe1-octreotide (TETA-OC) in rat liver and subsequent binding to superoxide dismutase (SOD) 4,6,7,17,18. The current study addresses this problem through investigation of a novel side-bridged macrocyclic chelator under the hypothesis that it may provide enhanced in vivo stability.…”

Section: Introductionmentioning

confidence: 95%

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A novel side-bridged hybrid phosphonate/acetate pendant cyclam: Synthesis, characterization, and 64Cu small animal PET imaging

Boswell

Regino

Baidoo

et al. 2009

Bioorganic & Medicinal Chemistry

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Copper-64 (t½ = 12.7 hr; β+: 0.653 MeV, 17.4%; β−: 0.578 MeV, 39%) is produced in a biomedical cyclotron and has applications in both imaging and therapy. Macrocyclic chelators are widely used as bifunctional chelators to bind copper radionuclides to antibodies and peptides owing to their relatively high kinetic stability. A novel side-bridged cyclam featuring both pendant acetate and phosphonate groups was synthesized using a Kabachnik-Fields approach followed by hydrobromic acid deprotection. The Cu(II) complex of the novel ligand was synthesized, radiolabeling with 64Cu was demonstrated, and in vitro (serum) stability was performed. In addition, in vivo distribution and clearance of the 64Cu-labeled complex was visualized by positron emission tomography (PET) imaging. This novel chelate may be useful in 64Cu-mediated diagnostic positron emission tomography (PET) imaging as well as targeted radiotherapeutic applications.

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Section: Resultssupporting

confidence: 82%

Section: Introductionmentioning

confidence: 95%

A novel side-bridged hybrid phosphonate/acetate pendant cyclam: Synthesis, characterization, and 64Cu small animal PET imaging

Boswell

Regino

Baidoo

et al. 2009

Bioorganic & Medicinal Chemistry

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“…Boswell et al directly compared the in vivo stability of CB-TE2A and CB-DO2A (32) which are analogues of TETA and DOTA respectively, and have developed the analytical conditions to purify and isolate the kinetic 64 Cu-CBcomplexes and their metabolic analytes [109,110]. Both CBligands were labeled in high radiochemical purity at 95°C using ethanol and cesium carbonate, followed by the addition of 64 CuCl 2 .…”

Section: The Cross-bridged Tetraamine Ligandsmentioning

confidence: 99%

Copper Chelation Chemistry and its Role in Copper Radiopharmaceuticals

Wadas

Wong²,

Weisman³

et al. 2007

CPD

259

314

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Molecular imaging is an important scientific discipline that plays a major role in clinical medicine and pharmaceutical development. While several imaging modalities including X-ray computed tomography (CT) and magnetic resonance imaging (MRI) generate high-resolution anatomical images, positron emission tomography (PET) and single photon emission computed tomography (SPECT) offer insight into the physiological processes that occur within a living organism. Of these two nuclear medicine imaging techniques, PET has advantages with respect to sensitivity and resolution, and this has led to the production and development of many positron emitting radionuclides that include non-traditional radionuclides of the transition metals. Copper-64 (t(1/2) = 12.7 h, beta(+): 17.4%, E(beta+max) = 656 keV; beta(-): 39%, E(beta-max) = 573 keV) has emerged as an important positron emitting radionuclide that has the potential for use in diagnostic imaging and radiotherapy. However, (64)Cu must be delivered to the living system as a stable complex that is attached to a biological targeting molecule for effective imaging and therapy. Therefore, significant research has been devoted to the development of ligands that can stably chelate (64)Cu. This review discusses the necessary characteristics of an effective (64)Cu chelator, while highlighting the development and evaluation of (64)Cu-complexes attached to biologically-targeted ligands.

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“…The stability of a radiopharmaceutical drug is usually analyzed in human serum and measured using radio-TLC, radio-HPLC and LC/MS. These techniques are based on the chromatographic separation of the radiolabeled compounds and their subsequent evaluation [13]. A very relevant field is radioimmunotherapy (RIT) using antibody-based labeled drugs.…”

Section: Radiotherapymentioning

confidence: 99%

Radiolabeling Strategies for Tumor-Targeting Proteinaceous Drugs

et al. 2014

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Owing to their large size proteinaceous drugs offer higher operative information content compared to the small molecules that correspond to the traditional understanding of druglikeness. As a consequence these drugs allow developing patient-specific therapies that provide the means to go beyond the possibilities of current drug therapy. However, the efficacy of these strategies, in particular "personalized medicine", depends on precise information about individual target expression rates. Molecular imaging combines non-invasive imaging methods with tools of molecular and cellular biology and thus bridges current knowledge to the clinical use. Moreover, nuclear medicine techniques provide therapeutic applications with tracers that behave like the diagnostic tracer. The advantages of radioiodination, still the most versatile radiolabeling strategy, and other labeled compounds comprising covalently attached radioisotopes are compared to the use of chelator-protein conjugates that are complexed with metallic radioisotopes. With the techniques using radioactive isotopes as a reporting unit or even the therapeutic principle, care has to be taken to avoid cleavage of the radionuclide from the protein it is linked to. The tracers used in molecular imaging require labeling techniques that provide site specific conjugation and metabolic stability. Appropriate choice of the radionuclide allows tailoring the properties of the labeled protein to the application required. Until the event of positron emission tomography the spectrum of nuclides used to visualize cellular and biochemical processes was largely restricted to iodine isotopes and 99m-technetium. Today, several nuclides such as 18-fluorine, 68-gallium and 86-yttrium have fundamentally extended the possibilities of tracer design and in turn caused the need for the development of chemical methods for their conjugation.

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Optimization of labeling and metabolite analysis of copper-64-labeled azamacrocyclic chelators by radio-LC-MS

Cited by 38 publications

References 26 publications

A novel side-bridged hybrid phosphonate/acetate pendant cyclam: Synthesis, characterization, and 64Cu small animal PET imaging

A novel side-bridged hybrid phosphonate/acetate pendant cyclam: Synthesis, characterization, and 64Cu small animal PET imaging

Copper Chelation Chemistry and its Role in Copper Radiopharmaceuticals

Radiolabeling Strategies for Tumor-Targeting Proteinaceous Drugs

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