Molecular imaging with copper-64

Smith, Suzanne V.

doi:10.1016/j.jinorgbio.2004.06.009

Cited by 210 publications

(164 citation statements)

References 142 publications

(306 reference statements)

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“…In particular, the published thermodynamic equilibrium constants suggest that 67 Cu-TETA would be less stable than 67 Cu-DTPA or 67 Cu-EDTA whereas 67 Cu-TETA was the only complex of the three to show any stability in serum. Such macrocyclic or macrobicyclic Cu 2+ complexes possess sufficiently high thermodynamic stability to allow efficient radiolabeling, as well as relatively rigid geometries that enhance their kinetic stability 8,10,75,76 . Individual bond dissociation is rapidly followed by recoordination, as the coordinating ligand remains spatially close to the metal centre.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous chelators have been reported for complexing copper [5][6][7][8][9][10][11][12][13][14][15][16] and several of these have been functionalized to allow attachment to antibodies [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and are now commercially available. The choice of antibody/BFC combination will affect efficacy as an imaging or therapy agent.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of ⁶⁴Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

et al. 2012

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High radiolabeling efficiency, preferably to high specific activity, and good stability of the radioimmunoconjugate are essential features for a successful immunoconjugate for imaging or therapy. In this study, the radiolabeling efficiency, in vitro stability and biodistribution of immunoconjugates with eight different bifunctional chelators labeled with 64 Cu were compared. The anti-CD20 antibody, rituximab, was conjugated to four macrocyclic bifunctional chelators (p-SCN-Bn-DOTA, p- , three DTPA derivatives (p-SCN-Bn-DTPA, p-SCN-CHX-A"-DTPA and ITC-2B3M-DTPA) and a macrobicyclic hexamine ("sarcophagine") chelator (sar-CO 2 H) = (1-NH 2 -8-NHCO(CH 2 ) 3 CO 2 H)sar where sar = sarcophagine = 3, 6,10,13,16,19-hexaazabicyclo[6.6.6]icosane). Radiolabeling efficiency under various conditions, in vitro stability in serum at 37°C and in vivo biodistribution and imaging in normal mice over 48 h were studied. All chelators except sar-CO 2 H were conjugated to rituximab by thiourea bond formation with an average of 4.9 +/− 0.9 chelators per antibody molecule. Sar-CO 2 H was conjugated to rituximab by amide bond formation with 0.5 chelators per antibody molecule. Efficiencies of 64 Cu radiolabeling were dependent on the concentration of immunoconjugate. Notably, the 64 Cu-NOTA-rituximab conjugate demonstrated highest radiochemical yield (95%) under very dilute conditions (31 nM NOTA-rituximab conjugate). Similarly, sar-CO-rituximab, containing 1/10 th the number of chelators per antibody compared to other conjugates retained high labeling efficiency (98 %) at an antibody concentration of 250 nM. In contrast to the radioimmunoconjugates containing DTPA derivatives, which demonstrated poor serum stability, all macrocyclic radioimmunoconjugates were very stable in serum with <6 % dissociation of 64 Cu over 48 h. In vivo biodistribution profiles in normal female Balb/C mice were similar for all the macrocyclic radioimmunoconjugates with most of the activity remaining in the blood pool up to 48 h. Whilst all the macrocyclic bifunctional chelators are suitable for molecular imaging using 64 Cu-labeled antibody conjugates, NOTA and sar-CO 2 H show significant advantages over the others in that they can be radiolabeled rapidly at room temperature, under dilute conditions resulting in high specific activity. Europe PMC Funders Group

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of ⁶⁴Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

et al. 2012

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“…Limitations to the chelating agents currently used with 64 Cu include significant loss of 64 Cu from the conjugate, leading to high uptake in the liver, and the requirement for postlabeling purification, typically by semipreparative HPLC. The further development of 64 Cu 2ϩ imaging agents therefore requires Cu(II) chelators with (i) greater in vivo stability, (ii) improved labeling properties, and (iii) simplified conjugation to targeting molecules, such as antibodies, antibody fragments, and peptides (5).…”

mentioning

confidence: 99%

“…The in vivo stability and high specificity for target antigens make mAbs attractive vehicles for tumor-specific targeting of PET radionuclides. Imaging with radiolabeled mAbs directed against tumorassociated antigens has, however, been hampered in part by the limited number of radionuclides developed for use in radioimmunodiagnosis (5). Recently, antibody fragments and engineered antibody derivatives such as divalent synthetic singlechain Fv antibodies have been constructed in an effort to accelerate clearance kinetics, while maintaining tumor target specificity (6).…”

mentioning

confidence: 99%

“…However, a major challenge to developing 64 Cu 2ϩ -based imaging agents has been identifying bifunctional chelating agents that stably complex 64 Cu 2ϩ under physiological conditions (5,10,11). Such copper chelators must form complexes with high thermodynamic and kinetic stability and be resistant to in vivo processes such as transchelation to endogenous copper transport and binding proteins, and reduction to Cu 1ϩ .…”

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confidence: 99%

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Positron emission tomography (PET) imaging of neuroblastoma and melanoma with ⁶⁴ Cu-SarAr immunoconjugates

Voss¹,

Smith

DiBartolo

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement 18 F-FDG. Copper-64 ( 64 Cu) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high in vivo lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1-N-(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosane-1,8-diamine) for use in developing a new class of tumorspecific 64 Cu radiopharmaceuticals for imaging neuroblastoma and melanoma. The anti-GD2 monoclonal antibody (mAb) 14.G2a, and its chimeric derivative, ch14.18, target disialogangliosides that are overexpressed on neuroblastoma and melanoma. Both mAbs were conjugated to SarAr using carbodiimide coupling. Radiolabeling with 64 Cu resulted in >95% of the 64 Cu being chelated by the immunoconjugate. Specific activities of at least 10 Ci/ g (1 Ci ‫؍‬ 37 GBq) were routinely achieved, and no additional purification was required after 64 Cu labeling. Solid-phase radioimmunoassays and intact cell-binding assays confirmed retention of bioactivity. Biodistribution studies in athymic nude mice bearing s.c. neuroblastoma (IMR-6, NMB-7) and melanoma (M21) xenografts showed that 15-20% of the injected dose per gram accumulated in the tumor at 24 hours after injection, and only 5-10% of the injected dose accumulated in the liver, a lower value than typically seen with other chelators. Uptake by a GD2-negative tumor xenograft was significantly lower (<5% injected dose per gram). MicroPET imaging confirmed significant uptake of the tracer in GD-2-positive tumors, with minimal uptake in GD-2-negative tumors and nontarget tissues such as liver. The 64 Cu-SarAr-mAb system described here is potentially applicable to 64 Cu-PET imaging with a broad range of antibody or peptide-based imaging agents.

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Radiolabeled Nanoplatforms: Imaging Hot Bullets Hitting their Target

Rossin

2011

Nanoplatform‐Based Molecular Imaging

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Nanomedicine is a rapidly evolving field. Every year, new and more sophisticated nanoplatforms (NPs) designed to deliver drugs to specific targets or for molecular imaging of disease states make their appearance on the scientific scene. The assessment of the in vivo distribution of these NPs is the first step in order to fully understand their potential as candidate nanomedicines and to predict and prevent toxic side effects. To this aim, the incorporation of a radionuclide in the NP is of great advantage, as radiometric assays are rapid and quantitative. Furthermore, noninvasive nuclear imaging techniques are highly sensitive, achieve high tissue penetration and good spatial resolution, and can accelerate the translation of new NPs into the clinic. This chapter gives an overview of the strategies to label NPs with a variety of radionuclides (radiometals and radiohalogens), focusing on some of the hurdles that scientists must overcome (or take into consideration) when administering these radioconjugates in vivo. Furthermore, the latest achievements in molecular imaging of angiogenesis with radiolabeled NPs are reviewed.The most recent publications on nanoplatforms labeled with ␥ -and ␤ + -emitting radionuclides for SPECT and PET imaging are reviewed. Different strategies to label nanoplatforms are described, particularly those involving radiometals ( 64 Cu, 111 In, 67/68 Ga, 86 Y, 99m Tc, and 186/188 Re) and radiohalogens ( 123/124/125/131 I, 76 B, and 18 F). Some of the problems occurring when evaluating radiolabeled nanoplatforms in vivo are also covered. Finally, the use of radiolabeled nanoplatforms for angiogenesis imaging with PET and SPECT is discussed.

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Molecular imaging with copper-64

Cited by 210 publications

References 142 publications

Comparison of ⁶⁴Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

Comparison of ⁶⁴Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

Positron emission tomography (PET) imaging of neuroblastoma and melanoma with ⁶⁴ Cu-SarAr immunoconjugates

Radiolabeled Nanoplatforms: Imaging Hot Bullets Hitting their Target

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Molecular imaging with copper-64

Cited by 210 publications

References 142 publications

Comparison of 64Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

Comparison of 64Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

Positron emission tomography (PET) imaging of neuroblastoma and melanoma with 64 Cu-SarAr immunoconjugates

Radiolabeled Nanoplatforms: Imaging Hot Bullets Hitting their Target

Contact Info

Product

Resources

About

Comparison of ⁶⁴Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

Comparison of ⁶⁴Cu-Complexing Bifunctional Chelators for Radioimmunoconjugation: Labeling Efficiency, Specific Activity, and in Vitro/in Vivo Stability

Positron emission tomography (PET) imaging of neuroblastoma and melanoma with ⁶⁴ Cu-SarAr immunoconjugates