Pharmacokinetics of the FO23C5 anti-CEA antibody fragment labelled with 99Tcm and 111In

Dj, Hnatowich; Mardirossian, G.; Rusckowski, Mary; Bushe, Harry; Tw, Griffin; Ab, Brill

doi:10.1097/00006231-199301000-00011

Cited by 7 publications

(2 citation statements)

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“…In all chromatograms other than those of the preparation itself (i.e., injectate) in saline, a peak appears in fraction 76. In the case of 99mTc and, most probably 188Re as well, this peak is due to radiolabeled cysteine produced by transchelation of the label from the fusion protein to this thiol (17)(18)(19). It may be estimated from Figure 3 that 22% of the 99mTc and 41% of 188Re were present as labeled cysteine at 24 h. The addition of biotinylated antibody to aliquots of the serum incubates in the case of both labels resulted in a shift to higher molecular weight.…”

Section: Radiolabeling Of Metallothionein-streptavidinmentioning

confidence: 99%

Recombinant Metallothionein-Conjugated Streptavidin Labeled with 188Re and 99mTc

Virzi¹,

Winnard²,

Fogarasi³

et al. 1995

Bioconjugate Chem.

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Consideration is now being given to the use of avidin (or streptavidin) and biotin for radiotherapy of tumor. Accordingly, the goal of this study was to radiolabel a mouse metallothionein-streptavidin fusion protein with 188Re and to compare its properties to those of the same fusion protein radiolabeled with 99mTc. A recombinant metallothionein-streptavidin fusion protein was radiolabeled by transchelation with 99mTc- and 188Re-glucoheptonate. Labeling efficiency, which was not optimized for either radionuclide, was approximately 60% for 99mTc and 20% for 188Re. Radiochemical purity was demonstrated by size exclusion HPLC both by nearly quantitative shifts of the 188Re label to higher molecular weight upon the addition of biotinylated antibody and by the absence of a shift with biotinsaturated 188Re-metallothionein-streptavidin. Stability of the labels in 37 degrees C serum was evaluated by comparing the HPLC radiochromatograms of serum samples both before and after the addition of biotinylated antibody. The 188Re label behaved like 99mTc in that the same peaks were evident, including one prominent peak due to labeled cysteine. Recoveries during HPLC analysis of serum samples showed that oxidation rates to perrhenate and pertechnetate were identical. However, instability to cysteine challenge was greater for 188Re; for example, the loss of label to cysteine after 24 h under one set of conditions was 41% for 188Re and 22% with 99mTc. Analysis by HPLC of liver and kidney homogenates from mice administered the labeled antibodies were qualitatively and, in large measure, quantitatively independent of label. Biodistributions at 5 h in normal mice were statistically identical between the two labels in blood and in most tissues. In conclusion, streptavidin may be radiolabeled with radiorhenium using recombinant mouse metallothionein as a bifunctional chelator, and under one set of labeling conditions at least, 188Re showed similar in vitro and in vivo behavior to that of 99mTc labeled to the same fusion protein.

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Section: Radiolabeling Of Metallothionein-streptavidinmentioning

confidence: 99%

Recombinant Metallothionein-Conjugated Streptavidin Labeled with 188Re and 99mTc

Virzi¹,

Winnard²,

Fogarasi³

et al. 1995

Bioconjugate Chem.

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“…The radionuclide distribution was determined from autoradiographs of tissue obtained from routine tumours after administration of 125I-labelled antibodies, and assumed as a basis for calculations on 2]1At and 90y. This assumption is not valid in many cases, as it has been shown that the distribution of radionuclide attached to antibody is dependent on the radionuclide and conjugation chemistry [62]. The dosimetric potential of autoradiography in determining the level of uptake in cell nuclei has been demonstrated by frozen section studies of 111ln-oxine labelled leucocytes.…”

Section: Microdosimetrymentioning

confidence: 99%

Radionuclide targeting and dosimetry at the microscopic level: the role of microautoradiography

Puncher

Blower

1994

Eur J Nucl Med

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The understanding of localisation mechanisms and microdosimetry of diagnostic and therapeutic radiopharmaceuticals depends on knowledge of their biodistribution at the microscopic level (cellular and subcellular) in the target tissues. Various methods have been advanced for obtaining information about this microdistribution: subcellular fractionation, secondary ion mass spectrometry imaging, microprobe elemental analysis in the electron microscope, and microautoradiography. This review compares these approaches, and discusses in detail the methodology of microautoradiography (the most generally useful approach) with imaging and therapy radionuclides. Literature examples of applications of microautoradiography in nuclear medicine are reviewed, and the future potential contribution of the techniques is assessed.

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Radiolabeling with technetium-99m to study high-capacity and low-capacity biochemical systems

Eckelman

1995

Eur J Nucl Med

106

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After a brief review of the history of the development of technetium-99m-labeled radiopharmaceuticals, the use of technetium chelates in high-capacity systems is discussed. The latter are used in the study of five organ systems, the kidneys, liver, bone, brain, and heart. The chemical characterization of 99mTc complexes is also reviewed, followed by discussion of the various approaches to the labeling of proteins with direct labeling, the preformed chelate approach, and the antibody chelator conjugate approach. Thereafter, the labeling of biochemicals with 99mTc for use with easily saturated sites, e.g., receptors and enzymes, is considered. Finally, attention is given to factors that affect the preparation of high specific activity, high affinity 99mTc-labeled biochemicals.

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Pharmacokinetics of the FO23C5 anti-CEA antibody fragment labelled with 99Tcm and 111In

Cited by 7 publications

References 0 publications

Recombinant Metallothionein-Conjugated Streptavidin Labeled with 188Re and 99mTc

Recombinant Metallothionein-Conjugated Streptavidin Labeled with 188Re and 99mTc

Radionuclide targeting and dosimetry at the microscopic level: the role of microautoradiography

Radiolabeling with technetium-99m to study high-capacity and low-capacity biochemical systems

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