Methods to avoid adverse effect of circulating antigen on biodistribution of 125I-labeled antiTac dsFv: Preinjection of intact antibody versus clearance of antigen with avidin-biotin system

Hisataka Kobayashi, Sun Bao-Fu, Tae M. Yoo, Le Nhat, Meyoung-Kon Kim, Chang H. Paik, Ira Pastan, Thomas A. Waldmann, Jorge A. Carrasquillo

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The presence of circulating antigen may adversely affect the biodistribution of a radiolabeled antibody. The α subunit of the interleukin-2 receptor (IL-2Rα) is a cell-surface receptor that is overexpressed in various hematologic malignancies and in benign disorders. This receptor is cleaved from the cell surface and can be found in high concentrations in serum. Radiolabeled antiTac antibodies are being evaluated to target this receptor. Previous studies have shown that circulating soluble IL-2Rα (sIL-2Rα)adversely affected the biodistribution of radiolabeled antiTac disulfide-stabilized (ds)Fv. In this study, we compared blocking and clearing sIL-2Rα to see which better minimized its interference with the biodistribution of radiolabeled antiTac dsFv. Methods: Two models of sIL- 2Rα were used: one consisted of mice given intravenous sIL-2Rα and the other consisted of mice bearing SP2/Tac tumor xenografts (IL-2Rα positive), which shed sIL-2Rα. We biotinylated humanized antiTac monoclonal antibody (bt-HuTac) and radiolabeled it with 125I. We then compared its biodistribution with that of humanized antiTac monoclonal antibody IgG (HuTac). We examined the biodistribution of an injected dose of 125I- labeled antiTac dsFv after a preinjection of HuTac to block the sIL-2Rα epitope and after a preinjection of bt-HuTac, followed by an avidin chase. Result: The 125I-labeled bt-HuTac cleared from the serum at a rate similar to that of HuTac. The avidin chase effectively cleared >92% of circulating125I-labeled bt-HuTac within 20 min and was also effective in clearing sIL-2Rα. In comparison, HuTac prolonged the retention of125I- labeled sIL-2Rα in the circulation, and the avidin chase decreased 125I- labeled sIL-2Rα to <18% of control. Although the two-step antigen-clearing system effectively cleared the antigen from the circulation and improved the biodistribution of125I- labeled dsFv, the HuTac preinjection method had a similar but longer lasting beneficial effect on 125I-labeled dsFv biodistribution. Conclusion: Preinjection of either HuTac or bt-HuTac with avidin chase improved the biodistribution of subsequently administered 125I-labeled antiTac dsFv by preventing the dsFv from binding to the sIL- 2Rα, but the HuTac blocking method is simpler and longer lasting.

Original languageEnglish
Pages (from-to)1381-1391
Number of pages11
JournalJournal of Nuclear Medicine
Volume40
Issue number8
Publication statusPublished - 1999 Aug 1
Externally publishedYes

Fingerprint

Avidin
Biotin
Interleukin-2 Receptors
Antibodies, Monoclonal, Humanized
Antigens
Antibodies
Cell Surface Receptors
Hematologic Neoplasms
Serum
Heterografts
Disulfides
Epitopes
Immunoglobulin G
Neoplasms

Keywords

  • Avidin
  • Fv fragment
  • Interleukin- 2
  • Monoclonal antibody
  • Radioimmunodetection

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Methods to avoid adverse effect of circulating antigen on biodistribution of 125I-labeled antiTac dsFv : Preinjection of intact antibody versus clearance of antigen with avidin-biotin system. / Kobayashi, Hisataka; Bao-Fu, Sun; Yoo, Tae M.; Nhat, Le; Kim, Meyoung-Kon; Paik, Chang H.; Pastan, Ira; Waldmann, Thomas A.; Carrasquillo, Jorge A.

In: Journal of Nuclear Medicine, Vol. 40, No. 8, 01.08.1999, p. 1381-1391.

Research output: Contribution to journalArticle

Kobayashi, Hisataka ; Bao-Fu, Sun ; Yoo, Tae M. ; Nhat, Le ; Kim, Meyoung-Kon ; Paik, Chang H. ; Pastan, Ira ; Waldmann, Thomas A. ; Carrasquillo, Jorge A. / Methods to avoid adverse effect of circulating antigen on biodistribution of 125I-labeled antiTac dsFv : Preinjection of intact antibody versus clearance of antigen with avidin-biotin system. In: Journal of Nuclear Medicine. 1999 ; Vol. 40, No. 8. pp. 1381-1391.
@article{858d1c439d18426781fcc66701f6eedf,
title = "Methods to avoid adverse effect of circulating antigen on biodistribution of 125I-labeled antiTac dsFv: Preinjection of intact antibody versus clearance of antigen with avidin-biotin system",
abstract = "The presence of circulating antigen may adversely affect the biodistribution of a radiolabeled antibody. The α subunit of the interleukin-2 receptor (IL-2Rα) is a cell-surface receptor that is overexpressed in various hematologic malignancies and in benign disorders. This receptor is cleaved from the cell surface and can be found in high concentrations in serum. Radiolabeled antiTac antibodies are being evaluated to target this receptor. Previous studies have shown that circulating soluble IL-2Rα (sIL-2Rα)adversely affected the biodistribution of radiolabeled antiTac disulfide-stabilized (ds)Fv. In this study, we compared blocking and clearing sIL-2Rα to see which better minimized its interference with the biodistribution of radiolabeled antiTac dsFv. Methods: Two models of sIL- 2Rα were used: one consisted of mice given intravenous sIL-2Rα and the other consisted of mice bearing SP2/Tac tumor xenografts (IL-2Rα positive), which shed sIL-2Rα. We biotinylated humanized antiTac monoclonal antibody (bt-HuTac) and radiolabeled it with 125I. We then compared its biodistribution with that of humanized antiTac monoclonal antibody IgG (HuTac). We examined the biodistribution of an injected dose of 125I- labeled antiTac dsFv after a preinjection of HuTac to block the sIL-2Rα epitope and after a preinjection of bt-HuTac, followed by an avidin chase. Result: The 125I-labeled bt-HuTac cleared from the serum at a rate similar to that of HuTac. The avidin chase effectively cleared >92{\%} of circulating125I-labeled bt-HuTac within 20 min and was also effective in clearing sIL-2Rα. In comparison, HuTac prolonged the retention of125I- labeled sIL-2Rα in the circulation, and the avidin chase decreased 125I- labeled sIL-2Rα to <18{\%} of control. Although the two-step antigen-clearing system effectively cleared the antigen from the circulation and improved the biodistribution of125I- labeled dsFv, the HuTac preinjection method had a similar but longer lasting beneficial effect on 125I-labeled dsFv biodistribution. Conclusion: Preinjection of either HuTac or bt-HuTac with avidin chase improved the biodistribution of subsequently administered 125I-labeled antiTac dsFv by preventing the dsFv from binding to the sIL- 2Rα, but the HuTac blocking method is simpler and longer lasting.",
keywords = "Avidin, Fv fragment, Interleukin- 2, Monoclonal antibody, Radioimmunodetection",
author = "Hisataka Kobayashi and Sun Bao-Fu and Yoo, {Tae M.} and Le Nhat and Meyoung-Kon Kim and Paik, {Chang H.} and Ira Pastan and Waldmann, {Thomas A.} and Carrasquillo, {Jorge A.}",
year = "1999",
month = "8",
day = "1",
language = "English",
volume = "40",
pages = "1381--1391",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "8",

}

TY - JOUR

T1 - Methods to avoid adverse effect of circulating antigen on biodistribution of 125I-labeled antiTac dsFv

T2 - Preinjection of intact antibody versus clearance of antigen with avidin-biotin system

AU - Kobayashi, Hisataka

AU - Bao-Fu, Sun

AU - Yoo, Tae M.

AU - Nhat, Le

AU - Kim, Meyoung-Kon

AU - Paik, Chang H.

AU - Pastan, Ira

AU - Waldmann, Thomas A.

AU - Carrasquillo, Jorge A.

PY - 1999/8/1

Y1 - 1999/8/1

N2 - The presence of circulating antigen may adversely affect the biodistribution of a radiolabeled antibody. The α subunit of the interleukin-2 receptor (IL-2Rα) is a cell-surface receptor that is overexpressed in various hematologic malignancies and in benign disorders. This receptor is cleaved from the cell surface and can be found in high concentrations in serum. Radiolabeled antiTac antibodies are being evaluated to target this receptor. Previous studies have shown that circulating soluble IL-2Rα (sIL-2Rα)adversely affected the biodistribution of radiolabeled antiTac disulfide-stabilized (ds)Fv. In this study, we compared blocking and clearing sIL-2Rα to see which better minimized its interference with the biodistribution of radiolabeled antiTac dsFv. Methods: Two models of sIL- 2Rα were used: one consisted of mice given intravenous sIL-2Rα and the other consisted of mice bearing SP2/Tac tumor xenografts (IL-2Rα positive), which shed sIL-2Rα. We biotinylated humanized antiTac monoclonal antibody (bt-HuTac) and radiolabeled it with 125I. We then compared its biodistribution with that of humanized antiTac monoclonal antibody IgG (HuTac). We examined the biodistribution of an injected dose of 125I- labeled antiTac dsFv after a preinjection of HuTac to block the sIL-2Rα epitope and after a preinjection of bt-HuTac, followed by an avidin chase. Result: The 125I-labeled bt-HuTac cleared from the serum at a rate similar to that of HuTac. The avidin chase effectively cleared >92% of circulating125I-labeled bt-HuTac within 20 min and was also effective in clearing sIL-2Rα. In comparison, HuTac prolonged the retention of125I- labeled sIL-2Rα in the circulation, and the avidin chase decreased 125I- labeled sIL-2Rα to <18% of control. Although the two-step antigen-clearing system effectively cleared the antigen from the circulation and improved the biodistribution of125I- labeled dsFv, the HuTac preinjection method had a similar but longer lasting beneficial effect on 125I-labeled dsFv biodistribution. Conclusion: Preinjection of either HuTac or bt-HuTac with avidin chase improved the biodistribution of subsequently administered 125I-labeled antiTac dsFv by preventing the dsFv from binding to the sIL- 2Rα, but the HuTac blocking method is simpler and longer lasting.

AB - The presence of circulating antigen may adversely affect the biodistribution of a radiolabeled antibody. The α subunit of the interleukin-2 receptor (IL-2Rα) is a cell-surface receptor that is overexpressed in various hematologic malignancies and in benign disorders. This receptor is cleaved from the cell surface and can be found in high concentrations in serum. Radiolabeled antiTac antibodies are being evaluated to target this receptor. Previous studies have shown that circulating soluble IL-2Rα (sIL-2Rα)adversely affected the biodistribution of radiolabeled antiTac disulfide-stabilized (ds)Fv. In this study, we compared blocking and clearing sIL-2Rα to see which better minimized its interference with the biodistribution of radiolabeled antiTac dsFv. Methods: Two models of sIL- 2Rα were used: one consisted of mice given intravenous sIL-2Rα and the other consisted of mice bearing SP2/Tac tumor xenografts (IL-2Rα positive), which shed sIL-2Rα. We biotinylated humanized antiTac monoclonal antibody (bt-HuTac) and radiolabeled it with 125I. We then compared its biodistribution with that of humanized antiTac monoclonal antibody IgG (HuTac). We examined the biodistribution of an injected dose of 125I- labeled antiTac dsFv after a preinjection of HuTac to block the sIL-2Rα epitope and after a preinjection of bt-HuTac, followed by an avidin chase. Result: The 125I-labeled bt-HuTac cleared from the serum at a rate similar to that of HuTac. The avidin chase effectively cleared >92% of circulating125I-labeled bt-HuTac within 20 min and was also effective in clearing sIL-2Rα. In comparison, HuTac prolonged the retention of125I- labeled sIL-2Rα in the circulation, and the avidin chase decreased 125I- labeled sIL-2Rα to <18% of control. Although the two-step antigen-clearing system effectively cleared the antigen from the circulation and improved the biodistribution of125I- labeled dsFv, the HuTac preinjection method had a similar but longer lasting beneficial effect on 125I-labeled dsFv biodistribution. Conclusion: Preinjection of either HuTac or bt-HuTac with avidin chase improved the biodistribution of subsequently administered 125I-labeled antiTac dsFv by preventing the dsFv from binding to the sIL- 2Rα, but the HuTac blocking method is simpler and longer lasting.

KW - Avidin

KW - Fv fragment

KW - Interleukin- 2

KW - Monoclonal antibody

KW - Radioimmunodetection

UR - http://www.scopus.com/inward/record.url?scp=0345425709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345425709&partnerID=8YFLogxK

M3 - Article

C2 - 10450692

AN - SCOPUS:0345425709

VL - 40

SP - 1381

EP - 1391

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 8

ER -