[Experimental data for administration of insulin-like growth factor 1 (IGF-1) and basic fibroblast growth factor (bFGF) for prevention of radiation myelopathy].
BACKGROUND
Current models of radiation myelopathy provide a rationale for growth factor-based prevention strategies. Thus, we tested whether insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) alone or in combination modulate radiation tolerance of the rat cervical spinal cord.


METHODS
The cervical spinal cord of 68 adult Fisher F344 rats received a total dose of 30-36 Gy, given as a single fraction of 16 Gy followed by a second radiation dose of 14-20 Gy. Continuous intrathecal infusion of bFGF (44 rats) or saline (24 rats) into the cisterna magna was given concomitantly. A further experiment included 14 additional rats which were treated with subcutaneous injection of IGF-1 parallel to irradiation with a total dose of 34 Gy or 36 Gy. 20 rats received combined treatment, i.e. intrathecal infusion of bFGF plus subcutaneous injection of IGF-1, starting 24 hours before irradiation (total dose 33 Gy or 36 Gy) for a total of 4 days. Animals were followed until myelopathy developed or for a maximum of 12 months. Histopathologic examinations were performed post mortem.


RESULTS
Treatment with bFGF alone or IGF-1 alone increased the median time to myelopathy significantly. In the 36-Gy group, after combination treatment a comparable prolongation of latency was seen. Moreover, rats treated with 33 Gy and combined bFGF plus IGF-1 showed a significantly reduced risk of myelopathy, too (p = 0.0015, Figures 1 and 2).


CONCLUSIONS
Combination of IGF-1 and bFGF was more potent than single agent treatment. We observed a significantly reduced myelopathy rate at an intermediate radiation dose level and a longer time to myelopathy at a high-dose level. This finding strengthens the evidence that brief therapeutic intervention can decrease radiation-induced neurotoxicity. Further studies will be undertaken to optimize this strategy.
Nieder
Carsten
C
Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Technische Universität, Klinikum rechts der Isar, München. nieder_radonc_tum@hotmail.com
Price
Roger E
RE
Rivera
Belinda
B
Andratschke
Nicolaus
N
Ang
K Kian
KK
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004359:Drug Therapy, Combination; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D011292:Premedication; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000473:pathology / Q000528:radiation effects*
D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I