No effect of the hemoglobin solution HBOC-201 on the response of the rat R1H tumor to fractionated irradiation.

Abstract

BACKGROUND AND PURPOSE:

Tumor hypoxia is regarded as one important underlying feature of radioresistance. The authors report on an experimental approach to improve tumor response to radiation by combining fractionated irradiation with HBOC-201, an ultrapurified polymerized hemoglobin solution, which is currently used in clinical phase II/III trials as alternative oxygen carrier and proved to be highly effective in tissue oxygenation (tpO(2)).

MATERIAL AND METHODS:

Subcutaneously growing rhabdomyosarcoma R1H tumors of the rat were treated with either 40 Gy (2 Gy/fraction, 20 fractions in 2 weeks, ambient) followed by graded top-up doses (clamped) alone, or in combination with HBOC-201, or with HBOC-201 plus carbogen (95% O(2) + 5% CO(2)). Local tumor control (TCD50%) and growth delay were used as endpoints. In addition, the effect of HBOC-201 alone or in combination with carbogen on the tpO(2) of tumor and muscle was determined using a flexible stationary probe (Licox, GMS).

RESULTS:

TCD50% values of 119 Gy (95% confidence interval 103;135), 111 Gy (84;138), and 102 Gy (83;120) were determined for tumors irradiated alone, in combination with HBOC-201, and with HBOC-201 plus carbogen, respectively. Although the dose-response curves showed a slight shift to lower doses when HBOC-201 or HBOC-201 plus carbogen was added, the differences in TCD50% were not statistically significant. No effect was seen on the growth delay of recurrent tumors. HBOC-201 alone did not effect tumor or muscle tpO(2). In combination with carbogen the mean tpO(2) of muscle raised from 23.9 mmHg to 59.3 mmHg (p < 0.05), but this effect was less pronounced than the increase in tpO(2) by carbogen alone.

CONCLUSION:

Low-dose application of HBOC-201 does not improve the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation.

• Authors: Annette Raabe, André Gottschalk, Matthias Hommel, Hans-Hermann Dubben, Thomas Strandl
• Journal: Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] (Strahlenther Onkol) Vol. 181 Issue 11 Pg. 730-7 (Nov 2005) ISSN: 0179-7158 [Print] Germany
• PMID: 16254709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Substitutes
• Hemoglobins
• Oxyhemoglobins
• HBOC 201

Topics

• Animals
• Blood Substitutes (pharmacology)
• Cell Division (radiation effects)
• Dose Fractionation, Radiation
• Hemoglobins (pharmacology)
• Oxygen Consumption
• Oxyhemoglobins (metabolism, radiation effects)
• Rats
• Rhabdomyosarcoma (pathology, radiotherapy)