Modulation of rodent spinal cord radiation tolerance by administration of platelet-derived growth factor.
OBJECTIVE
To examine the role of platelet-derived growth factor (PDGF) for ameliorating radiation myelopathy of the cervical spinal cord in a rodent model.


METHODS
After developing the technique for cannulation of the basal cistern, initial animal experiments were conducted to test the feasibility of intrathecal continuous infusion of PDGF in a model of cervical spinal cord irradiation in adult Fisher F-344 rats and to determine the most effective dose level of PDGF. Subsequently, the dose-modification factor was determined in a larger group of rats. Irradiation was given in 2 fractions (16 Gy followed by 14-24 Gy) and animals were examined for the development of paresis.


RESULTS
The initial dose-finding experiment revealed significant differences in the incidence of radiation myelopathy (100% in saline-treated control rats, 25% with the most effective dose of PDGF, up to 100% with less effective doses). The most effective dose of PDGF was 0.014 mug per day. Subsequent experiments revealed a median effective dose (ED(50)) of 35.6 Gy (95% confidence interval, 34.7-36.5 Gy) for animals receiving this dose of PDGF in contrast to 33.8 Gy (33.4-34.3 Gy) for the control group (p = 0.003). The dose-modification factor obtained with this dose of PDGF was 1.05.


CONCLUSIONS
Intrathecal administration of PDGF concomitant to irradiation of the cervical spinal cord in rats was feasible. Treatment with PDGF significantly increased the tolerance of the spinal cord. The PDGF experiments should be viewed as a proof of principle that brief therapeutic intervention in the earliest phase of damage induction can reduce late effects in the spinal cord. They form the basis for further studies of growth factor administration in this particular model.
Andratschke
Nicolaus H
NH
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Nieder
Carsten
C
Price
Roger E
RE
Rivera
Belinda
B
Tucker
Susan L
SL
Ang
K Kian
KK
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D007278:Injections, Spinal; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000528:radiation effects*
D010982:Platelet-Derived Growth Factor; D011837:Radiation-Protective Agents