Effects of radiolysis on Yttrium-90-labeled Lym-1 antibody preparations

Q. A. Salako, Robert T O'Donnell, S. J. DeNardo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The physical half-life of 2.6 days and 2.2 MeV beta emissions of 90Y provide excellent properties for radioimmunotherapy applications. However, the clinically useful beta particles may be a source of radiation-induced damage of 90-labeled immunoconjugate radiopharmaceuticals during preparation or short-term storage. The stability of 90Y-labeled Lym-1 antibody was studied in standard radiopharmacy conditions to establish a formulation at which radiolysis is not a problem. Methods: Lym-1-2IT-BAD immunoconjugate intermediate was prepared according to our standard procedure, then labeled with 90Y at 1, 2, 4 and 9.4 mCi/mg Lym-1 using 0.5 M tetramethylammonium acetate, pH 7, labeling buffer. Each mixture was challenged in diethylenetriaminepentaacetic acid to remove nonspecifically bound 90Y. The 90Y-2IT-BAD-Lym-1 products were purified by centrifuged molecular sieving column chromatography. The radiochemical purity and immunoreactivity of each preparation was monitored daily by high-performance liquid chromatography (HPLC) and solid-phase radioimmunoassay, respectively, for 3 days. The preparation at 2 mCi/mg was also formulated in 4% (wt/vol) human serum albumin (HSA) overall and at 9.4 mCi/mg in five-fold water, 4 and 10% (wt/vol) HSA overall; all were monitored as above. Results: The monomeric quality and purity profile of products at 1 and 2 mCi/mg were retained (≤ 80%) as was their immunoreactivity (≤ 75%) over 3 days. The radiochemical purity and immunoreactivity of the product at 4 mCi/mg declined to 65% and 28%, respectively, by 3 days after preparation and in just 48 hr, the product at 9.4 mCi/mg had degraded to 21% in radiochemical purity with only 3% immunoreactivity. The current HPLC data and earlier published chromatographic evidence did not support a compromised radiochemical integrity of 90Y-DOTA complexes by loss of 90Y from the DOTA chelate. Conclusion: Radiolysis of 90Y-labeled antibody preparations did not appear to be a problem at 90Y- 2IT-BAD-Lym-1 products ≤ 2 mCi/mg. Human serum albumin proved to be an effective radioprotectant as the initial 100% immunoreactivity of the product at 2 mCi/mg was retained for 72 hr. The results underscore the need for appropriate formulations and dilutions of clinical doses of 90Y immunopharmaceuticals immediately after manufacture.

Original languageEnglish (US)
Pages (from-to)667-670
Number of pages4
JournalJournal of Nuclear Medicine
Volume39
Issue number4
StatePublished - Apr 1998

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Yttrium
Serum Albumin
Immunoconjugates
Antibodies
High Pressure Liquid Chromatography
Beta Particles
Radioimmunotherapy
Radiopharmaceuticals
Radioimmunoassay
Half-Life
Chromatography
Buffers
Acetates
Radiation
Acids
Water
2IT-BAD-Lym-1 monoclonal antibody

Keywords

  • Antibody
  • Radiolysis
  • Radioprotectant
  • Yttrium-90

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Effects of radiolysis on Yttrium-90-labeled Lym-1 antibody preparations. / Salako, Q. A.; O'Donnell, Robert T; DeNardo, S. J.

In: Journal of Nuclear Medicine, Vol. 39, No. 4, 04.1998, p. 667-670.

Research output: Contribution to journalArticle

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title = "Effects of radiolysis on Yttrium-90-labeled Lym-1 antibody preparations",
abstract = "The physical half-life of 2.6 days and 2.2 MeV beta emissions of 90Y provide excellent properties for radioimmunotherapy applications. However, the clinically useful beta particles may be a source of radiation-induced damage of 90-labeled immunoconjugate radiopharmaceuticals during preparation or short-term storage. The stability of 90Y-labeled Lym-1 antibody was studied in standard radiopharmacy conditions to establish a formulation at which radiolysis is not a problem. Methods: Lym-1-2IT-BAD immunoconjugate intermediate was prepared according to our standard procedure, then labeled with 90Y at 1, 2, 4 and 9.4 mCi/mg Lym-1 using 0.5 M tetramethylammonium acetate, pH 7, labeling buffer. Each mixture was challenged in diethylenetriaminepentaacetic acid to remove nonspecifically bound 90Y. The 90Y-2IT-BAD-Lym-1 products were purified by centrifuged molecular sieving column chromatography. The radiochemical purity and immunoreactivity of each preparation was monitored daily by high-performance liquid chromatography (HPLC) and solid-phase radioimmunoassay, respectively, for 3 days. The preparation at 2 mCi/mg was also formulated in 4{\%} (wt/vol) human serum albumin (HSA) overall and at 9.4 mCi/mg in five-fold water, 4 and 10{\%} (wt/vol) HSA overall; all were monitored as above. Results: The monomeric quality and purity profile of products at 1 and 2 mCi/mg were retained (≤ 80{\%}) as was their immunoreactivity (≤ 75{\%}) over 3 days. The radiochemical purity and immunoreactivity of the product at 4 mCi/mg declined to 65{\%} and 28{\%}, respectively, by 3 days after preparation and in just 48 hr, the product at 9.4 mCi/mg had degraded to 21{\%} in radiochemical purity with only 3{\%} immunoreactivity. The current HPLC data and earlier published chromatographic evidence did not support a compromised radiochemical integrity of 90Y-DOTA complexes by loss of 90Y from the DOTA chelate. Conclusion: Radiolysis of 90Y-labeled antibody preparations did not appear to be a problem at 90Y- 2IT-BAD-Lym-1 products ≤ 2 mCi/mg. Human serum albumin proved to be an effective radioprotectant as the initial 100{\%} immunoreactivity of the product at 2 mCi/mg was retained for 72 hr. The results underscore the need for appropriate formulations and dilutions of clinical doses of 90Y immunopharmaceuticals immediately after manufacture.",
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N2 - The physical half-life of 2.6 days and 2.2 MeV beta emissions of 90Y provide excellent properties for radioimmunotherapy applications. However, the clinically useful beta particles may be a source of radiation-induced damage of 90-labeled immunoconjugate radiopharmaceuticals during preparation or short-term storage. The stability of 90Y-labeled Lym-1 antibody was studied in standard radiopharmacy conditions to establish a formulation at which radiolysis is not a problem. Methods: Lym-1-2IT-BAD immunoconjugate intermediate was prepared according to our standard procedure, then labeled with 90Y at 1, 2, 4 and 9.4 mCi/mg Lym-1 using 0.5 M tetramethylammonium acetate, pH 7, labeling buffer. Each mixture was challenged in diethylenetriaminepentaacetic acid to remove nonspecifically bound 90Y. The 90Y-2IT-BAD-Lym-1 products were purified by centrifuged molecular sieving column chromatography. The radiochemical purity and immunoreactivity of each preparation was monitored daily by high-performance liquid chromatography (HPLC) and solid-phase radioimmunoassay, respectively, for 3 days. The preparation at 2 mCi/mg was also formulated in 4% (wt/vol) human serum albumin (HSA) overall and at 9.4 mCi/mg in five-fold water, 4 and 10% (wt/vol) HSA overall; all were monitored as above. Results: The monomeric quality and purity profile of products at 1 and 2 mCi/mg were retained (≤ 80%) as was their immunoreactivity (≤ 75%) over 3 days. The radiochemical purity and immunoreactivity of the product at 4 mCi/mg declined to 65% and 28%, respectively, by 3 days after preparation and in just 48 hr, the product at 9.4 mCi/mg had degraded to 21% in radiochemical purity with only 3% immunoreactivity. The current HPLC data and earlier published chromatographic evidence did not support a compromised radiochemical integrity of 90Y-DOTA complexes by loss of 90Y from the DOTA chelate. Conclusion: Radiolysis of 90Y-labeled antibody preparations did not appear to be a problem at 90Y- 2IT-BAD-Lym-1 products ≤ 2 mCi/mg. Human serum albumin proved to be an effective radioprotectant as the initial 100% immunoreactivity of the product at 2 mCi/mg was retained for 72 hr. The results underscore the need for appropriate formulations and dilutions of clinical doses of 90Y immunopharmaceuticals immediately after manufacture.

AB - The physical half-life of 2.6 days and 2.2 MeV beta emissions of 90Y provide excellent properties for radioimmunotherapy applications. However, the clinically useful beta particles may be a source of radiation-induced damage of 90-labeled immunoconjugate radiopharmaceuticals during preparation or short-term storage. The stability of 90Y-labeled Lym-1 antibody was studied in standard radiopharmacy conditions to establish a formulation at which radiolysis is not a problem. Methods: Lym-1-2IT-BAD immunoconjugate intermediate was prepared according to our standard procedure, then labeled with 90Y at 1, 2, 4 and 9.4 mCi/mg Lym-1 using 0.5 M tetramethylammonium acetate, pH 7, labeling buffer. Each mixture was challenged in diethylenetriaminepentaacetic acid to remove nonspecifically bound 90Y. The 90Y-2IT-BAD-Lym-1 products were purified by centrifuged molecular sieving column chromatography. The radiochemical purity and immunoreactivity of each preparation was monitored daily by high-performance liquid chromatography (HPLC) and solid-phase radioimmunoassay, respectively, for 3 days. The preparation at 2 mCi/mg was also formulated in 4% (wt/vol) human serum albumin (HSA) overall and at 9.4 mCi/mg in five-fold water, 4 and 10% (wt/vol) HSA overall; all were monitored as above. Results: The monomeric quality and purity profile of products at 1 and 2 mCi/mg were retained (≤ 80%) as was their immunoreactivity (≤ 75%) over 3 days. The radiochemical purity and immunoreactivity of the product at 4 mCi/mg declined to 65% and 28%, respectively, by 3 days after preparation and in just 48 hr, the product at 9.4 mCi/mg had degraded to 21% in radiochemical purity with only 3% immunoreactivity. The current HPLC data and earlier published chromatographic evidence did not support a compromised radiochemical integrity of 90Y-DOTA complexes by loss of 90Y from the DOTA chelate. Conclusion: Radiolysis of 90Y-labeled antibody preparations did not appear to be a problem at 90Y- 2IT-BAD-Lym-1 products ≤ 2 mCi/mg. Human serum albumin proved to be an effective radioprotectant as the initial 100% immunoreactivity of the product at 2 mCi/mg was retained for 72 hr. The results underscore the need for appropriate formulations and dilutions of clinical doses of 90Y immunopharmaceuticals immediately after manufacture.

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