Enhanced kidney clearance with an ester-linked 99mTc-radiolabeled antibody Fab'-chelator conjugate

Weber, Robert; Boutin, Raymond H.; Nedelman, Mark; Lister‐James, John; Dean, Richard T.

doi:10.1021/bc00006a010

Cited by 45 publications

(40 citation statements)

References 14 publications

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“…Both sFv' species have C-terminal Gly4Cys as a peptide chelate, which was chosen to provide for N3S coordination of 99mTc. Mercaptoacetyltriglycine is another such N3S chelate (22) that is used in renal imaging and is the moiety that coordinates 99mTc within the RP-1 bifunctional chelate (23). These N3S chelates typically coordinate 99mTc as oxotechnetium, forming a square planar complex (22,24).…”

Section: Resultsmentioning

confidence: 99%

Radiometal labeling of recombinant proteins by a genetically engineered minimal chelation site: technetium-99m coordination by single-chain Fv antibody fusion proteins through a C-terminal cysteinyl peptide.

George

Jamar

Tai

et al. 1995

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

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We describe a method to facilitate radioimaging with technetium-99m (99mTc) by genetic incorporation of a 99mTc chelation site in recombinant single-chain Fv (sFv) antibody proteins. This method relies on fusion of the sFv C terminus with a Gly4Cys peptide that specifically coordinates 99mTc. By using analogues of the 26-10 anti-digoxin sFv as our primary model, we find that addition of the chelate peptide, to form 26-10-1 sFv', does not alter the antigen-binding affinity of sFv. We have demonstrated nearly quantitative chelation of 0.5-50 mCi of 99mTc per mg of 26-10-1 sFv' (1 Ci = 37 GBq). These 99mTc-labeled sFv' complexes are highly stable to challenge with saline buffers, plasma, or diethylenetriaminepentaacetic acid. We find that the 99mTc-labeled 741F8-1 sFv', specific for the c-erbB-2 tumor-associated antigen, is effective in imaging human ovarian carcinoma in a scid mouse tumor xenograft model. This fusion chelate methodology should be applicable to diagnostic imaging with 99mTc and radioimmunotherapy with 186Re or 188Re, and its use could extend beyond the sFv' to other engineered antibodies, recombinant proteins, and synthetic peptides.

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Section: Resultsmentioning

confidence: 99%

Radiometal labeling of recombinant proteins by a genetically engineered minimal chelation site: technetium-99m coordination by single-chain Fv antibody fusion proteins through a C-terminal cysteinyl peptide.

George

Jamar

Tai

et al. 1995

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

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“…The synthesis of the ciprofloxacin prodrug was based on two previous publications (Weber et al 1990; Hennard et al 2001). The biotinylated prodrug and biotinylated fluorescent analogue were synthesized by coupling a commercially available biotinylation reagent to maleimides of either the prodrug or fluorescein via glutathione.…”

Section: Methodsmentioning

confidence: 99%

Aggregatibacter actinomycetemcomitansbiofilm killing by a targeted ciprofloxacin prodrug

et al. 2013

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A pH-sensitive ciprofloxacin prodrug was synthesized and targeted against biofilms of the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa). The dose required to reduce the viability of a mature biofilm of Aa by ~80% was in the range of ng cm−2 of colonized area (mean biofilm density 2.33 x109 cells cm−2). A mathematical model was formulated that predicts the temporal change in the concentration of ciprofloxacin in the Aa biofilm as the drug is released and diffuses into the bulk medium. The predictions of the model were consistent with the extent of killing obtained. The results demonstrate the feasibility of the strategy to induce mortality, and together with the mathematical model, provide the basis for design of targeted antimicrobial prodrugs for the topical treatment of oral infections such as periodontitis. The targeted prodrug approach offers the possibility of optimizing the dose of available antimicrobials in order to kill a chosen pathogen while leaving the commensal microbiota relatively undisturbed.

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“…In radiolabeled polypeptides such as antibodies, an interposition of an enzyme-cleavable linkage between a polypeptide and a radiolabel constitutes a strategy to reduce the radioactivity in nontarget tissues [31][32][33] . However, since mannosylated compounds target similar cell types in both the target (SLN) and non-target (injection site), this strategy would result in similar clearance of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 11 radioactivity from both tissues, as observed with 125 I-NMA (Table 1).…”

Section: Mmentioning

confidence: 99%

Injection Site Radioactivity of ^99mTc-Labeled Mannosylated Dextran for Sentinel Lymph Node Mapping

et al. 2014

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The high and persistent radioactivity at the injection site hinders the accuracy and expansion of sentinel lymph node (SLN) mapping. We investigated the mechanism underlying the undesirable radioactivity after subcutaneous injection of (99m)Tc-labeled mannosylated dextran ((99m)Tc(CO)3-DCM20), a SLN mapping agent targeting mannose receptors on macrophages and dendritic cells, in a mouse model. Biodistribution studies were performed 1 h after subcutaneous injection of (99m)Tc(CO)3-DCM20 from the rear footpad of mice in the presence of varying molar amounts of DCM20 or DC15, a modified dextran without mannose. Biodistribution studies were also conducted after subcutaneous injection of [(125)I]radioiodinated mannosyl-neoglycoalbumin ((125)I-NMA) from the rear footpad. The distribution of fluorescence-labeled DCM20 and DC15 at the injection site was also compared 1 h after subcutaneous injection by immunofluorescent histochemistry. The radioactivity levels of (99m)Tc(CO)3-DCM20 at the injection site and popliteal lymph node, a SLN in this model, decreased with an increase in the molar amounts of DCM20, whereas no significant changes in biodistribution were observed after injection of (99m)Tc(CO)3-DCM20 with varying molar amounts of DC15. (125)I-NMA exhibited rapid elimination of radioactivity from both the popliteal lymph node and the injection site. The fluorescence-labeled DCM20 colocalized well with CD68-positive cells such as macrophages and dendritic cells at the injection site. While partial colocalization was observed between DC15 and CD68-positive cells, the signal intensity was very weak. These findings suggest that specific binding of (99m)Tc(CO)3-DCM20 to the mannose receptor on macrophages and dendritic cells would be responsible for the sustained radioactivity levels at the injection site. These results also imply that discriminated blockage of (99m)Tc(CO)3-DCM20 binding to mannose receptors at the injection sites would reduce the radioactivity at the injection site.

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Enhanced kidney clearance with an ester-linked 99mTc-radiolabeled antibody Fab'-chelator conjugate

Cited by 45 publications

References 14 publications

Radiometal labeling of recombinant proteins by a genetically engineered minimal chelation site: technetium-99m coordination by single-chain Fv antibody fusion proteins through a C-terminal cysteinyl peptide.

Radiometal labeling of recombinant proteins by a genetically engineered minimal chelation site: technetium-99m coordination by single-chain Fv antibody fusion proteins through a C-terminal cysteinyl peptide.

Aggregatibacter actinomycetemcomitansbiofilm killing by a targeted ciprofloxacin prodrug

Injection Site Radioactivity of ^99mTc-Labeled Mannosylated Dextran for Sentinel Lymph Node Mapping

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Enhanced kidney clearance with an ester-linked 99mTc-radiolabeled antibody Fab'-chelator conjugate

Cited by 45 publications

References 14 publications

Radiometal labeling of recombinant proteins by a genetically engineered minimal chelation site: technetium-99m coordination by single-chain Fv antibody fusion proteins through a C-terminal cysteinyl peptide.

Radiometal labeling of recombinant proteins by a genetically engineered minimal chelation site: technetium-99m coordination by single-chain Fv antibody fusion proteins through a C-terminal cysteinyl peptide.

Aggregatibacter actinomycetemcomitansbiofilm killing by a targeted ciprofloxacin prodrug

Injection Site Radioactivity of 99mTc-Labeled Mannosylated Dextran for Sentinel Lymph Node Mapping

Contact Info

Product

Resources

About

Injection Site Radioactivity of ^99mTc-Labeled Mannosylated Dextran for Sentinel Lymph Node Mapping