[186Re]-labeled mouse and chimeric monoclonal antibody 323/A3: A comparison of the efficacy in experimental human ovarian cancer

Els Kievit, Frank B. Van Gog, Hennie M.M. Schlüper, Guus A.M.S. Van Dongen, Herbert M. Pinedo, Epie Boven

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We have investigated whether [186-Re]-labeled chimeric monoclonal antibody 323/A3 (MAb c-323/A3) is as effective as [186Re]-labeled mouse 323/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xenografts OVCAR-3 and FMa. [186Re] was conjugated to MAbs with the use of the chelate S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3). The maximum number of metal-MAG3 groups that could be conjugated to one MAb molecule accepting a minimal initial increase of the blood clearance (15%) was 8.5 and 2.9 for c-323/A3 and m-323/A3, respectively. With these molar ratios the immunoreactivity of both MAbs was maintained. An inverse relationship was observed between the protein dose of c-323/A3 and its blood clearance. Both [186Re]-c-323/A3 and [186Re]-m-323/A3 were comparable in the inhibition of the tumor growth when higher protein doses were used. Together with the expected lower immunogenicity, our results imply that c-323/A3 is preferable for use in [186Re]-radioimmunotherapy in ovarian cancer patients.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalNuclear Medicine and Biology
Volume25
Issue number1
DOIs
Publication statusPublished - 1 Jan 1998

Cite this

@article{a9c8a0deffe549a8ac928b73e4354209,
title = "[186Re]-labeled mouse and chimeric monoclonal antibody 323/A3: A comparison of the efficacy in experimental human ovarian cancer",
abstract = "We have investigated whether [186-Re]-labeled chimeric monoclonal antibody 323/A3 (MAb c-323/A3) is as effective as [186Re]-labeled mouse 323/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xenografts OVCAR-3 and FMa. [186Re] was conjugated to MAbs with the use of the chelate S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3). The maximum number of metal-MAG3 groups that could be conjugated to one MAb molecule accepting a minimal initial increase of the blood clearance (15{\%}) was 8.5 and 2.9 for c-323/A3 and m-323/A3, respectively. With these molar ratios the immunoreactivity of both MAbs was maintained. An inverse relationship was observed between the protein dose of c-323/A3 and its blood clearance. Both [186Re]-c-323/A3 and [186Re]-m-323/A3 were comparable in the inhibition of the tumor growth when higher protein doses were used. Together with the expected lower immunogenicity, our results imply that c-323/A3 is preferable for use in [186Re]-radioimmunotherapy in ovarian cancer patients.",
keywords = "[Re], Mouse and Chimeric MAb 323/A3, Ovarian cancer, Radioimmunotherapy",
author = "Els Kievit and {Van Gog}, {Frank B.} and Schl{\"u}per, {Hennie M.M.} and {Van Dongen}, {Guus A.M.S.} and Pinedo, {Herbert M.} and Epie Boven",
year = "1998",
month = "1",
day = "1",
doi = "10.1016/S0969-8051(97)00154-6",
language = "English",
volume = "25",
pages = "37--45",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "1",

}

[186Re]-labeled mouse and chimeric monoclonal antibody 323/A3 : A comparison of the efficacy in experimental human ovarian cancer. / Kievit, Els; Van Gog, Frank B.; Schlüper, Hennie M.M.; Van Dongen, Guus A.M.S.; Pinedo, Herbert M.; Boven, Epie.

In: Nuclear Medicine and Biology, Vol. 25, No. 1, 01.01.1998, p. 37-45.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - [186Re]-labeled mouse and chimeric monoclonal antibody 323/A3

T2 - A comparison of the efficacy in experimental human ovarian cancer

AU - Kievit, Els

AU - Van Gog, Frank B.

AU - Schlüper, Hennie M.M.

AU - Van Dongen, Guus A.M.S.

AU - Pinedo, Herbert M.

AU - Boven, Epie

PY - 1998/1/1

Y1 - 1998/1/1

N2 - We have investigated whether [186-Re]-labeled chimeric monoclonal antibody 323/A3 (MAb c-323/A3) is as effective as [186Re]-labeled mouse 323/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xenografts OVCAR-3 and FMa. [186Re] was conjugated to MAbs with the use of the chelate S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3). The maximum number of metal-MAG3 groups that could be conjugated to one MAb molecule accepting a minimal initial increase of the blood clearance (15%) was 8.5 and 2.9 for c-323/A3 and m-323/A3, respectively. With these molar ratios the immunoreactivity of both MAbs was maintained. An inverse relationship was observed between the protein dose of c-323/A3 and its blood clearance. Both [186Re]-c-323/A3 and [186Re]-m-323/A3 were comparable in the inhibition of the tumor growth when higher protein doses were used. Together with the expected lower immunogenicity, our results imply that c-323/A3 is preferable for use in [186Re]-radioimmunotherapy in ovarian cancer patients.

AB - We have investigated whether [186-Re]-labeled chimeric monoclonal antibody 323/A3 (MAb c-323/A3) is as effective as [186Re]-labeled mouse 323/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xenografts OVCAR-3 and FMa. [186Re] was conjugated to MAbs with the use of the chelate S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3). The maximum number of metal-MAG3 groups that could be conjugated to one MAb molecule accepting a minimal initial increase of the blood clearance (15%) was 8.5 and 2.9 for c-323/A3 and m-323/A3, respectively. With these molar ratios the immunoreactivity of both MAbs was maintained. An inverse relationship was observed between the protein dose of c-323/A3 and its blood clearance. Both [186Re]-c-323/A3 and [186Re]-m-323/A3 were comparable in the inhibition of the tumor growth when higher protein doses were used. Together with the expected lower immunogenicity, our results imply that c-323/A3 is preferable for use in [186Re]-radioimmunotherapy in ovarian cancer patients.

KW - [Re]

KW - Mouse and Chimeric MAb 323/A3

KW - Ovarian cancer

KW - Radioimmunotherapy

UR - http://www.scopus.com/inward/record.url?scp=0031986250&partnerID=8YFLogxK

U2 - 10.1016/S0969-8051(97)00154-6

DO - 10.1016/S0969-8051(97)00154-6

M3 - Article

VL - 25

SP - 37

EP - 45

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 1

ER -