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


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.


CONCLUSIONS
Low-dose application of HBOC-201 does not improve the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation.
Raabe
Annette
A
Department of Radiotherapy and Radiation Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. araabe@uke.uni-hamburg.de
Gottschalk
André
A
Hommel
Matthias
M
Dubben
Hans-Hermann
HH
Strandl
Thomas
T
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D002455:Cell Division / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D006454:Hemoglobins / Q000494:pharmacology*; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000378:metabolism / Q000528:radiation effects; D051381:Rats; D012208:Rhabdomyosarcoma / Q000473:pathology / Q000532:radiotherapy*
D001802:Blood Substitutes; D006454:Hemoglobins; D010108:Oxyhemoglobins; C096798:HBOC 201