PEG-hemoglobin

Effects on tumor oxygenation and radiosensitization

Beverly A. Teicher, Gulshan Ara, Ying Nan Chen, Yasunori Emi, Yoshihiro Kakeji, Masahiko Ikebe, Yoshihiko Maehara

Research output: Contribution to journalArticle

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Abstract

Derivatization with polyethylene glycol (PEG) is a biocompatible method to improve the therapeutic benefit of administered proteins by increasing their biological half-life. The ability of a PEG-bovine hemoglobin preparation (2-8 ml/kg) to increase the oxygen content of hypoxic tumor regions was determined in rats bearing the 13762 mammary carcinoma using an Eppendorf pO2 histograph. Administration of PEG-hemoglobin decreased the percent of pO2 readings ≤ 5 mmHg in animals breathing air or breathing carbogen, respectively. In rats, PEG-hemoglobin has a circulating half-life of 20 hr. A single administration of PEG-hemoglobin was able to provide increased tumor oxygenation on the following at least 3 days if atmospheres of 28% oxygen or carbogen were breathed. PEG-hemoglobin administration along with fractionated radiation therapy (2, 3 or 4 Gy x 5) resulted in radiation dose modifying factors of 1.2 ± 0.2, 1.4 ± 0.2 and 1.5 ± 0.2 when the animals breathed air, 28% oxygen or carbogen prior to and during radiation delivery, respectively. Using the EMT-6 murine mammary carcinoma tumor cell survival assay, administration of PEG-hemoglobin (6 ml/kg) prior to single dose radiation therapy resulted in dose modifying factors of 1.4 ± 0.2 1.8 ± 0.2 and 1.9 ± 0.2 when the animals breathed air, 28% oxygen or carbogen prior to and during radiation delivery, respectively. In EMT-6 tumor growth delay, administration of PEG-hemoglobin (6 ml/kg) along with fractionated radiation therapy (2, 3 or 4 Gy x 5) resulted in dose modifying factors of 1.2 ± 0.2, 1.5 ± 0.2 and 1.7 ± 0.2 when the animals breathed air, 28% oxygen or carbogen prior to and during radiation delivery. Administration of PEG-hemoglobin only on the first treatment day of a 5-day fractionated radiation therapy regimen resulted in dose modifying factors of 1.3 ± 0.2 and 1.4 ± 0.2 if the animals breathed 28% oxygen or carbogen prior to and during each radiation fraction delivery. Further investigation of this potentially clinically important oxygen delivery agent is warranted.

Original languageEnglish
Pages (from-to)200-210
Number of pages11
JournalRadiation Oncology Investigations
Volume4
Issue number5
DOIs
Publication statusPublished - Dec 1 1996

Fingerprint

oxygenation
hemoglobin
glycols
polyethylenes
Hemoglobins
tumors
Oxygen
animals
delivery
Neoplasms
oxygen
Radiation
radiation therapy
Radiotherapy
dosage
Air
radiation
air
Breast Neoplasms
breathing

All Science Journal Classification (ASJC) codes

  • Radiological and Ultrasound Technology
  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

PEG-hemoglobin : Effects on tumor oxygenation and radiosensitization. / Teicher, Beverly A.; Ara, Gulshan; Chen, Ying Nan; Emi, Yasunori; Kakeji, Yoshihiro; Ikebe, Masahiko; Maehara, Yoshihiko.

In: Radiation Oncology Investigations, Vol. 4, No. 5, 01.12.1996, p. 200-210.

Research output: Contribution to journalArticle

Teicher, Beverly A. ; Ara, Gulshan ; Chen, Ying Nan ; Emi, Yasunori ; Kakeji, Yoshihiro ; Ikebe, Masahiko ; Maehara, Yoshihiko. / PEG-hemoglobin : Effects on tumor oxygenation and radiosensitization. In: Radiation Oncology Investigations. 1996 ; Vol. 4, No. 5. pp. 200-210.
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