The binding of calcium and yttrium ions to a glycoprotein from bovine cortical bone

Williams, P.; Peacocke, A. R.

doi:10.1042/bj1051177

Cited by 38 publications

(14 citation statements)

References 21 publications

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“…The WBAR results also demonstrate uptake in the perimeter of the bones in areas outside rapid proliferative activity that is characteristic of the bone marrow. Thus, this uptake pattern is more similar to the reported wY uptake in the cortex (Williams and Peacock, 1964).…”

Section: Discussionsupporting

confidence: 88%

“…This is critically important for therapeutic radionuclides, since deposition of these radiometals in the bone will lead to a higher risk of myelosuppression, and thus may limit RAIT applications. Radionuclides with natural bone-seeking properties, such as 90Y (Williams and Peacock, 1964) will present special problems. If the 90Y remains firmly bound to the antibody, exposure of the marrow will occur principally as the labelled antibody in the blood passes through the sinuses of the bones.…”

Section: Discussionmentioning

confidence: 99%

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Selection of a dtpa chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice

Sharkey

Motta-Hennessy

Gansow

et al. 1990

Intl Journal of Cancer

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Our previous studies with a 90Y-labelled antibody against carcinoembryonic antigen (CEA) conjugated to the cyclic anhydride-DTPA (CA-DTPA) indicated that the accretion of 90Y in the bone may limit the application of 90Y-labelled antibodies for therapy. In this report, we have compared the tumor targeting of CA-DTPA-conjugated antibody to antibody conjugated with 4 isothiocyanatobenzyl (ITC-Bz) derivatives of DTPA in nude mice bearing a human colonic tumor xenograft. In biodistribution studies using an 111In-labelled anti-CEA murine monoclonal antibody (MAb), the CA-DTPA-conjugated MAb showed lower tumor uptake, faster blood clearance, and higher accretion in the liver than any of the 4 ITC-Bz-DTPA-conjugated MAbs. There were smaller differences among the 4 ITC-Bz-DTPA conjugates. Whole-body autoradiography of animals given 90Y-MAb prepared with the CA-DTPA or the ITC-Bz-DTPA showed less radioactivity in the bone with the ITC-Bz-DTPA-MAb than the CA-DTPA-MAb. 90Y uptake in the bone corresponded with regions of low proliferative activity as defined by 3H-labelled thymidine, suggesting that the 90Y was in the cortex rather than the marrow. These studies clearly show an advantage of the ITC-Bz-DTPA derivatives for 90Y and 111In labelling of MAbs.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Selection of a dtpa chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice

Sharkey

Motta-Hennessy

Gansow

et al. 1990

Intl Journal of Cancer

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“…One of these glycoproteins, alpha 2HS-glycoprotein, is derived from blood plasma and becomes incorporated into bone matrix during its formation [13,[15][16][17]. Another identified as a very acidic sialoprotein [18][19][20][21] is probably not blood borne and is particularly enriched in bone matrix [22]. Both have been reported to contain fucose residues, whereas collagen does not contain fucose [23].…”

Section: Discussionmentioning

confidence: 98%

Radioautographic visualization of3H-fucose incorporation into glycoprotein by osteoblasts and its deposition into bone matrix

Weinstock

1979

Calcif Tissue Int

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Summary. The elaboration of bone matrix glycoprotein by osteoblasts of alveolar bone was investigated by radioautography after the intravenous injection of 3H-fucose into young rats. At selected times after injection, animals were sacrificed by intracardiac perfusion and demineralized specimens were prepared for light and electron microscope radioautography.At 5 and 10 min after injection, when the blood fucose level was high, silver grains were restricted to the spheroidal and cylindrical saccules of the Golgi apparatus. At 20 min membrane-limited secretory granules were also labeled. By 35 min, the blood fucose level had dropped and silver grains were detected over the apical cortical cytoplasm, in association with secretory granules located therein. Some grains were present over osteoblast processes and the adjacent prebone matrix. By 4 h most of the silver grains had left the cell. At that time they were observed over prebone, adjacent to osteoblast processes, as well as over the prebone-bone junction where a distinct band of label was noted. In demineralized preparations an electron-dense granular material was present at the prebone-bone junction in association with collagen fibrils.These findings provide evidence that osteoblasts in alveolar bone synthesize fucose-containing glycoprotein and indicate that the addition of 3H-fucose occurs in the Golgi apparatus. The glycoprotein passes to the apical cortical cytoplasm by way of membrane-limited secretory granules, is exteriorized, and accumulates at the site where prebone transforms into bone (the prebone-bone junction). Since this is also the site of the calcification front, the deposition of labeled glycoprotein may be related to the deposition of bone mineral.Send offprint requests to M. Weinstock at the above address,

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“…It appears that the marrow's vascular space is not the most significant radiation source organ in patients treated with "Y-labelled MAbs. Yttrium-90 is a known bone-seeking element (Williams and Peacock, 1967) and this has been observed in mice following the administration of '%-labelled MAbs (Sharkey et al, 1988). If the radiation dose to the marrow for a given toxicity is the same in patients receiving 9OY-and 1311-labelled MAbs, then the radiation dose from bone is 4 to 6 times that from the marrow's vascular compartment in patients receiving "Y-labelled MAbs.…”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal131I- and90-labelled monoclonal antibodies for ovarian cancer: Pharmacokinetics and normal tissue dosimetry

Stewart¹,

Hird²,

Snook³

et al. 1988

Int. J. Cancer

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The pharmacokinetics of intraperitoneal (i.p.) radiolabelled monoclonal antibody (MAb) was studied in 35 patients receiving 40 i.p. injections. Eleven patients received 131I‐labelled MAb, 24 received 90Y‐labelled MAb, and 5 patients received a second 131I MAb treatment after having developed human anti‐mouse antibodies (HAMA). All patients had blood and urine isotope activity monitored for 5 days after MAb injection. The radiation dose to bone marrow from the vascular compartment in the marrow was calculated by applying the MIRD formula to the measured blood activity. In HAMA negative patients, peak blood isotope activity was observed at 40 hr post injection with a mean of 26% and 21% of the injected 131I and 90Y activity respectively. Sixty‐five percent of the injected 131I activity, but only 12% of the administered 90Y, was excreted in the urine. Myelosuppression limited the administered 131I and 90Y activities to below 160 and 20 mCi respectively. In patients receiving 131I labelled MAbs, the marrow is irradiated by MAb within its circulation, producing myelosuppression that can be predicted by applying the MIRD formula to the blood isotope activity. This is not true for 90Y‐labelled MAbs, where bone absorption of yttrium (which cannot be measured in patients) is the dominant radiation source for bone‐marrow irradiation. Patients with HAMA present clear 131 MAb rapidly with a decreased radiation dose to marrow and reduced myelosuppression. Giving patients intravenous antimouse immunoglobulin to clear 131I‐labelled MAb absorbed from the peritoneal cavity could decrease the toxicity observed in these patients. Patients receiving 90Y DTPA‐chelated MAbs are unlikely to benefit, as catabolized yttrium is not excreted, and is concentrated in liver, spleen and bone. On the other hand, the use of i.v. chelating agents such as EDTA may scavenge non‐protein‐bound (90Y with increased excretion in the urine and less myelosuppression.

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The binding of calcium and yttrium ions to a glycoprotein from bovine cortical bone

Cited by 38 publications

References 21 publications

Selection of a dtpa chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice

Selection of a dtpa chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice

Radioautographic visualization of3H-fucose incorporation into glycoprotein by osteoblasts and its deposition into bone matrix

Intraperitoneal131I- and90-labelled monoclonal antibodies for ovarian cancer: Pharmacokinetics and normal tissue dosimetry

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