Biodistribution and dosimetry of pretargeted monoclonal antibody 2D12.5 and Y-Janus-DOTA in BALB/c mice with KHJJ mouse adenocarcinoma

S. P. Lubic, D. A. Goodwin, C. F. Meares, C. Song, M. Osen, M. Hays

Research output: Contribution to journalArticle

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Abstract

Biodistribution and dosimetry of 88Y (and equimolar 90Y) Janusdodecanetetraacetic acid (DOTA) were performed using a three-step pretargeting protocol in BALB/c mice bearing mouse mammary adenocarcinoma (KHJJ) implants. Pretargeting was performed with mouse monoclonal antibody (mAb) 2D12.5 specific for yttrium-DOTA, and the chase was Y-DOTA-human transferrin conjugate. In this article, we report extensive organ dosimetry and the theoretic limits of the radionuclide physical half-life (Tp) for pretargeting. Methods: Organ biodistribution data were obtained from bioassays on tissue taken from tumor mice killed at 3, 24, 48, 72, 96, and 120 h after intravenous injection of 88Y-Janus-DOTA. Uptake and retention of 88Y as a function of time were described by nonlinear least squares fits of the tissue data to multiexponential functions. Radiation dose estimates for equivalent molar amounts of 90Y were subsequently derived from these time-integrated functions. Results: The results were as follows: rapid blood clearance of 88Y-Janus-DOTA; rapid uptake and slow clearance of 88Y-Janus-DOTA from the tumor over 5 d; rapid clearance from all organs and body; largest radiation absorbed dose (AD) per injected dose of 63.52 (cGy/MBq) to tumor; high therapeutic ratios (AD tumor/AD tissue), particularly for blood and bone; and optimal radionuclide Tp range from 30 min to 10 d. Conclusion: Although the absolute concentration of 90Y in the tumor is less using the hapten system than is achieved generally with the chelated radionuclide covalently attached to the mAb, the achievable tumor uptake of radioactivity, coupled with low radioactivity in bone, blood, and other organs, suggests that a three-step pretargeting protocol has considerable promise as a method for 90Y radioimmunotherapy.

Original languageEnglish (US)
Pages (from-to)670-678
Number of pages9
JournalJournal of Nuclear Medicine
Volume42
Issue number4
StatePublished - 2001
Externally publishedYes

Fingerprint

Adenocarcinoma
Monoclonal Antibodies
Radioisotopes
Neoplasms
Radioactivity
Radiation
Radioimmunotherapy
Yttrium
Bone and Bones
Haptens
Transferrin
Least-Squares Analysis
Intravenous Injections
Biological Assay
Half-Life
yttrium(III)-1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid
Breast
Therapeutics

Keywords

  • In pretargeting
  • Y
  • Biodistribution
  • Dosimetry
  • Radioimmunoimaging
  • Radioimmunotherapy
  • Therapeutic ratio

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Biodistribution and dosimetry of pretargeted monoclonal antibody 2D12.5 and Y-Janus-DOTA in BALB/c mice with KHJJ mouse adenocarcinoma. / Lubic, S. P.; Goodwin, D. A.; Meares, C. F.; Song, C.; Osen, M.; Hays, M.

In: Journal of Nuclear Medicine, Vol. 42, No. 4, 2001, p. 670-678.

Research output: Contribution to journalArticle

Lubic, S. P. ; Goodwin, D. A. ; Meares, C. F. ; Song, C. ; Osen, M. ; Hays, M. / Biodistribution and dosimetry of pretargeted monoclonal antibody 2D12.5 and Y-Janus-DOTA in BALB/c mice with KHJJ mouse adenocarcinoma. In: Journal of Nuclear Medicine. 2001 ; Vol. 42, No. 4. pp. 670-678.
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T1 - Biodistribution and dosimetry of pretargeted monoclonal antibody 2D12.5 and Y-Janus-DOTA in BALB/c mice with KHJJ mouse adenocarcinoma

AU - Lubic, S. P.

AU - Goodwin, D. A.

AU - Meares, C. F.

AU - Song, C.

AU - Osen, M.

AU - Hays, M.

PY - 2001

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AB - Biodistribution and dosimetry of 88Y (and equimolar 90Y) Janusdodecanetetraacetic acid (DOTA) were performed using a three-step pretargeting protocol in BALB/c mice bearing mouse mammary adenocarcinoma (KHJJ) implants. Pretargeting was performed with mouse monoclonal antibody (mAb) 2D12.5 specific for yttrium-DOTA, and the chase was Y-DOTA-human transferrin conjugate. In this article, we report extensive organ dosimetry and the theoretic limits of the radionuclide physical half-life (Tp) for pretargeting. Methods: Organ biodistribution data were obtained from bioassays on tissue taken from tumor mice killed at 3, 24, 48, 72, 96, and 120 h after intravenous injection of 88Y-Janus-DOTA. Uptake and retention of 88Y as a function of time were described by nonlinear least squares fits of the tissue data to multiexponential functions. Radiation dose estimates for equivalent molar amounts of 90Y were subsequently derived from these time-integrated functions. Results: The results were as follows: rapid blood clearance of 88Y-Janus-DOTA; rapid uptake and slow clearance of 88Y-Janus-DOTA from the tumor over 5 d; rapid clearance from all organs and body; largest radiation absorbed dose (AD) per injected dose of 63.52 (cGy/MBq) to tumor; high therapeutic ratios (AD tumor/AD tissue), particularly for blood and bone; and optimal radionuclide Tp range from 30 min to 10 d. Conclusion: Although the absolute concentration of 90Y in the tumor is less using the hapten system than is achieved generally with the chelated radionuclide covalently attached to the mAb, the achievable tumor uptake of radioactivity, coupled with low radioactivity in bone, blood, and other organs, suggests that a three-step pretargeting protocol has considerable promise as a method for 90Y radioimmunotherapy.

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