Coordinating Radiometals of Copper, Gallium, Indium, Yttrium, and Zirconium for PET and SPECT Imaging of Disease

Wadas, Thaddeus J.; Wong, Edward H.; Weisman, Gary R.; Anderson, Carolyn J.

doi:10.1021/cr900325h

Cited by 807 publications

(953 citation statements)

References 530 publications

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“…Exchanging Gd 3+ for 68 Ga would also allow imaging with PET (23). As an MRI gene reporter the construct described here has a number of advantages over those described previously.…”

Section: Discussionmentioning

confidence: 99%

Dual-modality gene reporter for in vivo imaging

Patrick

Hammersley

Loizou

et al. 2013

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

129

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The ability to track cells and their patterns of gene expression in living organisms can increase our understanding of tissue development and disease. Gene reporters for bioluminescence, fluorescence, radionuclide, and magnetic resonance imaging (MRI) have been described but these suffer variously from limited depth penetration, spatial resolution, and sensitivity. We describe here a gene reporter, based on the organic anion transporting protein Oatp1a1, which mediates uptake of a clinically approved, Gd3+-based, hepatotrophic contrast agent (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid). Cells expressing the reporter showed readily reversible, intense, and positive contrast (up to 7.8-fold signal enhancement) in T1-weighted magnetic resonance images acquired in vivo. The maximum signal enhancement obtained so far is more than double that produced by MRI gene reporters described previously. Exchanging the Gd3+ ion for the radionuclide, 111In, also allowed detection by single-photon emission computed tomography, thus combining the spatial resolution of MRI with the sensitivity of radionuclide imaging.

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“…Exchanging Gd 3+ for 68 Ga would also allow imaging with PET (23). As an MRI gene reporter the construct described here has a number of advantages over those described previously.…”

Section: Discussionmentioning

confidence: 99%

Dual-modality gene reporter for in vivo imaging

Patrick

Hammersley

Loizou

et al. 2013

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

129

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“…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%

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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“…The isotope 89 Zr is one of several positron-emitting radiometals that are increasing in popularity as radiolabels for positron emission tomography (PET) [1][2][3][4][5]. A search of the PubMed database [6] found over 55 publications with 89 Zr mentioned in the title, 75% of which had been published since 2009.…”

Section: Introductionmentioning

confidence: 99%

Routine Production of 89Zr Using an Automated Module

et al. 2013

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89Zr has emerged as a useful radioisotope for targeted molecular imaging via positron emission tomography (PET) in both animal models and humans. This isotope is particularly attractive for cancer research because its half-life (t 1/2 = 3.27 days) is well-suited for in vivo targeting of macromolecules and nanoparticles to cell surface antigens expressed by cancer cells. Furthermore, 89Zr emits a low-energy positron (E β+,mean = 0.40 MeV), which is favorable for high spatial resolution in PET, with an adequate branching ratio for positron emission (BR = 23%). The demand for 89 Zr for research purposes is increasing; however, 89Zr also emits significant gamma radiation (Γ 15 keV = 6.6 Rcm 2 /mCih), which makes producing large amounts of this isotope by hand unrealistic from a radiation safety standpoint. Fortunately, a straightforward method exists for production of Zr safely and routinely, at activities in excess of 50 mCi, with radionuclidic purity > 99.9% and satisfactory effective specific activity (ESA).

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Coordinating Radiometals of Copper, Gallium, Indium, Yttrium, and Zirconium for PET and SPECT Imaging of Disease

Cited by 807 publications

References 530 publications

Dual-modality gene reporter for in vivo imaging

Dual-modality gene reporter for in vivo imaging

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

Routine Production of 89Zr Using an Automated Module

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Coordinating Radiometals of Copper, Gallium, Indium, Yttrium, and Zirconium for PET and SPECT Imaging of Disease

Cited by 807 publications

References 530 publications

Dual-modality gene reporter for in vivo imaging

Dual-modality gene reporter for in vivo imaging

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

Routine Production of 89Zr Using an Automated Module

Contact Info

Product

Resources

About

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