High dose rhenium-186-labeling of monoclonal antibodies for clinical application pitfalls and solutions

Frank B. Van Gog, G. W M Visser, J. W G Stroomer, Jan C. Roos, Gordon B. Snow, G. A M S Van Dongen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND. Rhenium-186 (186Re) has ideal properties for adjuvant radioimmunotherapy (RIT). However, the lack of suitable methods for high dose 186Re labeling of monoclonal antibodies (MAbs) has hampered the use of 186Re in clinical RIT. After development of a chemically identical multistep procedure for the production of 186Re-MAG3-MAb and 99mTc/99Tc-MAG3-MAb conjugates for use as a matched pair, the authors now report on further progress to make this labeling method broadly applicable for high dose 186Re labeling. METHODS. The number of metal- MAG3 groups that can be coupled to a MAb without alteration of the biodistribution was investigated by radioimmunoscintigraphy (RIS) in patients with head and neck squamous cell carcinoma (HNSCC). For labeling with 500 mCi [186Re]ReO4/-, an efficient chemoprotection was introduced to suppress the damaging effects of radiation during conjugation and conjugate purification. Furthermore, the authors developed strategies that make the procedure easy and safe to perform at any medical center. RESULTS. MAbs showed a minor variation in biodistribution in HNSCC patients when the number of metal-chelate groups per MAb varied between <1 and 4.3. High dose 186Re-MAb conjugates (150-250 mCi) with a Re-MAG3:MAb ratio of 3.4 were obtained with a radiochemical purity of >95% and minimal aggregate formation (≤6%). Furthermore, a semiautomated labeling device and a convenient 100 mCi labeling kit in the form of a dried 186Re- MAG3-TFP ester were developed. RIT studies in HNSCC-bearing nude mice showed that high dose 186Re-labeled MAb U36 is more effective than iodine-131-labeled MAb U36. CONCLUSIONS. High dose 186Re-MAb conjugates were prepared that exhibit an optimal stability, immunoreactivity, and pharmacokinetic behavior. The availability of a kit procedure for coupling 186Re to MAbs might open the possibility of a broad application of 186Re in RIT.

LanguageEnglish
Pages2360-2370
Number of pages11
JournalCancer
Volume80
Issue number12 SUPPL.
Publication statusPublished - 15 Dec 1997

Cite this

Van Gog, Frank B. ; Visser, G. W M ; Stroomer, J. W G ; Roos, Jan C. ; Snow, Gordon B. ; Van Dongen, G. A M S. / High dose rhenium-186-labeling of monoclonal antibodies for clinical application pitfalls and solutions. In: Cancer. 1997 ; Vol. 80, No. 12 SUPPL. pp. 2360-2370.
@article{b5e6be29ce5743928e593ff45db73ce5,
title = "High dose rhenium-186-labeling of monoclonal antibodies for clinical application pitfalls and solutions",
abstract = "BACKGROUND. Rhenium-186 (186Re) has ideal properties for adjuvant radioimmunotherapy (RIT). However, the lack of suitable methods for high dose 186Re labeling of monoclonal antibodies (MAbs) has hampered the use of 186Re in clinical RIT. After development of a chemically identical multistep procedure for the production of 186Re-MAG3-MAb and 99mTc/99Tc-MAG3-MAb conjugates for use as a matched pair, the authors now report on further progress to make this labeling method broadly applicable for high dose 186Re labeling. METHODS. The number of metal- MAG3 groups that can be coupled to a MAb without alteration of the biodistribution was investigated by radioimmunoscintigraphy (RIS) in patients with head and neck squamous cell carcinoma (HNSCC). For labeling with 500 mCi [186Re]ReO4/-, an efficient chemoprotection was introduced to suppress the damaging effects of radiation during conjugation and conjugate purification. Furthermore, the authors developed strategies that make the procedure easy and safe to perform at any medical center. RESULTS. MAbs showed a minor variation in biodistribution in HNSCC patients when the number of metal-chelate groups per MAb varied between <1 and 4.3. High dose 186Re-MAb conjugates (150-250 mCi) with a Re-MAG3:MAb ratio of 3.4 were obtained with a radiochemical purity of >95{\%} and minimal aggregate formation (≤6{\%}). Furthermore, a semiautomated labeling device and a convenient 100 mCi labeling kit in the form of a dried 186Re- MAG3-TFP ester were developed. RIT studies in HNSCC-bearing nude mice showed that high dose 186Re-labeled MAb U36 is more effective than iodine-131-labeled MAb U36. CONCLUSIONS. High dose 186Re-MAb conjugates were prepared that exhibit an optimal stability, immunoreactivity, and pharmacokinetic behavior. The availability of a kit procedure for coupling 186Re to MAbs might open the possibility of a broad application of 186Re in RIT.",
keywords = "Re- labeling kit, Re-labeled monoclonal antibody, Tc-labeled monoclonal antibody, Head and neck cancer, Radioimmnoscintigraphy, Radioimmunotheraphy",
author = "{Van Gog}, {Frank B.} and Visser, {G. W M} and Stroomer, {J. W G} and Roos, {Jan C.} and Snow, {Gordon B.} and {Van Dongen}, {G. A M S}",
year = "1997",
month = "12",
day = "15",
language = "English",
volume = "80",
pages = "2360--2370",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "12 SUPPL.",

}

Van Gog, FB, Visser, GWM, Stroomer, JWG, Roos, JC, Snow, GB & Van Dongen, GAMS 1997, 'High dose rhenium-186-labeling of monoclonal antibodies for clinical application pitfalls and solutions', Cancer, vol. 80, no. 12 SUPPL., pp. 2360-2370.

High dose rhenium-186-labeling of monoclonal antibodies for clinical application pitfalls and solutions. / Van Gog, Frank B.; Visser, G. W M; Stroomer, J. W G; Roos, Jan C.; Snow, Gordon B.; Van Dongen, G. A M S.

In: Cancer, Vol. 80, No. 12 SUPPL., 15.12.1997, p. 2360-2370.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - High dose rhenium-186-labeling of monoclonal antibodies for clinical application pitfalls and solutions

AU - Van Gog, Frank B.

AU - Visser, G. W M

AU - Stroomer, J. W G

AU - Roos, Jan C.

AU - Snow, Gordon B.

AU - Van Dongen, G. A M S

PY - 1997/12/15

Y1 - 1997/12/15

N2 - BACKGROUND. Rhenium-186 (186Re) has ideal properties for adjuvant radioimmunotherapy (RIT). However, the lack of suitable methods for high dose 186Re labeling of monoclonal antibodies (MAbs) has hampered the use of 186Re in clinical RIT. After development of a chemically identical multistep procedure for the production of 186Re-MAG3-MAb and 99mTc/99Tc-MAG3-MAb conjugates for use as a matched pair, the authors now report on further progress to make this labeling method broadly applicable for high dose 186Re labeling. METHODS. The number of metal- MAG3 groups that can be coupled to a MAb without alteration of the biodistribution was investigated by radioimmunoscintigraphy (RIS) in patients with head and neck squamous cell carcinoma (HNSCC). For labeling with 500 mCi [186Re]ReO4/-, an efficient chemoprotection was introduced to suppress the damaging effects of radiation during conjugation and conjugate purification. Furthermore, the authors developed strategies that make the procedure easy and safe to perform at any medical center. RESULTS. MAbs showed a minor variation in biodistribution in HNSCC patients when the number of metal-chelate groups per MAb varied between <1 and 4.3. High dose 186Re-MAb conjugates (150-250 mCi) with a Re-MAG3:MAb ratio of 3.4 were obtained with a radiochemical purity of >95% and minimal aggregate formation (≤6%). Furthermore, a semiautomated labeling device and a convenient 100 mCi labeling kit in the form of a dried 186Re- MAG3-TFP ester were developed. RIT studies in HNSCC-bearing nude mice showed that high dose 186Re-labeled MAb U36 is more effective than iodine-131-labeled MAb U36. CONCLUSIONS. High dose 186Re-MAb conjugates were prepared that exhibit an optimal stability, immunoreactivity, and pharmacokinetic behavior. The availability of a kit procedure for coupling 186Re to MAbs might open the possibility of a broad application of 186Re in RIT.

AB - BACKGROUND. Rhenium-186 (186Re) has ideal properties for adjuvant radioimmunotherapy (RIT). However, the lack of suitable methods for high dose 186Re labeling of monoclonal antibodies (MAbs) has hampered the use of 186Re in clinical RIT. After development of a chemically identical multistep procedure for the production of 186Re-MAG3-MAb and 99mTc/99Tc-MAG3-MAb conjugates for use as a matched pair, the authors now report on further progress to make this labeling method broadly applicable for high dose 186Re labeling. METHODS. The number of metal- MAG3 groups that can be coupled to a MAb without alteration of the biodistribution was investigated by radioimmunoscintigraphy (RIS) in patients with head and neck squamous cell carcinoma (HNSCC). For labeling with 500 mCi [186Re]ReO4/-, an efficient chemoprotection was introduced to suppress the damaging effects of radiation during conjugation and conjugate purification. Furthermore, the authors developed strategies that make the procedure easy and safe to perform at any medical center. RESULTS. MAbs showed a minor variation in biodistribution in HNSCC patients when the number of metal-chelate groups per MAb varied between <1 and 4.3. High dose 186Re-MAb conjugates (150-250 mCi) with a Re-MAG3:MAb ratio of 3.4 were obtained with a radiochemical purity of >95% and minimal aggregate formation (≤6%). Furthermore, a semiautomated labeling device and a convenient 100 mCi labeling kit in the form of a dried 186Re- MAG3-TFP ester were developed. RIT studies in HNSCC-bearing nude mice showed that high dose 186Re-labeled MAb U36 is more effective than iodine-131-labeled MAb U36. CONCLUSIONS. High dose 186Re-MAb conjugates were prepared that exhibit an optimal stability, immunoreactivity, and pharmacokinetic behavior. The availability of a kit procedure for coupling 186Re to MAbs might open the possibility of a broad application of 186Re in RIT.

KW - Re- labeling kit

KW - Re-labeled monoclonal antibody

KW - Tc-labeled monoclonal antibody

KW - Head and neck cancer

KW - Radioimmnoscintigraphy

KW - Radioimmunotheraphy

UR - http://www.scopus.com/inward/record.url?scp=0031444654&partnerID=8YFLogxK

M3 - Article

VL - 80

SP - 2360

EP - 2370

JO - Cancer

T2 - Cancer

JF - Cancer

SN - 0008-543X

IS - 12 SUPPL.

ER -