[131I]- and [125I]metaiodobenzylguanidine therapy in macroscopic and microscopic tumors: A comparative study in SK-N-SH human neuroblastoma and PC12 rat pheochromocytoma xenografts
✍ Scribed by Marja Rutgers; Corine K.M. Buitenhuis; Martin A. van der Valk; Cees A. Hoefnagel; P.A. Voûte; Lou A. Smets
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- French
- Weight
- 389 KB
- Volume
- 90
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
131 I]Metaiodobenzylguanidine ([ 131 I]MIBG) targeted radiotherapy is effective in debulking childhood neuroblastoma. The high-energy beta-emitter [ 131 I]MIBG is, however, not very well suited to treat submillimeter tumors. The [ 125 I]MIBG emission is more fully absorbed in small target volumes and therefore advocated for treatment of microscopic neuroblastoma. We investigated whether i.v. [ 125 I]MIBG can have a therapeutic advantage over i.v. [ 131 I]MIBG in realistic animal models. We used BALB/c nu/nu mice, bearing neuroadrenergic xenografts which differ in MIBG handling, i.e., extragranular vs. granular MIBG storage in the SK-N-SH human neuroblastoma and PC12 rat pheochromocytoma, respectively. Groups of 4-9 animals were treated with 10-100 MBq radioiodinated MIBG. Responses were calibrated against the effect of 4-5 Gy of external beam X-rays. Subcutaneous xenografts: Due to the more extensive MIBG accumulation, the estimated MIBG exposure of the PC12 tumor was nearly 20-fold higher compared with the SK-N-SH xenograft which corresponded with a marked, i.e., nine-fold increased tumor growth delay after radioiodinated MIBG therapy. Both xenografts were equally sensitive to high-dose rate local irradiation. In neuroblastoma as well as pheochromocytoma, the therapeutic efficacy of [ 131 I]MIBG was 6 times higher compared to the [ 125 I]MIBG which is in reasonable agreement with the reported "131-I over 125-I" ratio of approximately 9 for the calculated absorbed radiation doses per unit of radioactivity. Apparently, the neuroblastoma was not relatively more sensitive to the (ultra)short range emitter [ 125 I]MIBG than the pheochromocytoma, indicating that its therapeutic efficacy is independent of the intracellular MIBG storage mode. Microscopic tumors: The pheochromocytoma model consisted of widespread disease after i.v. cell injection with survival as endpoint. For the neuroblastoma, we induced focal intrahepatic microscopic tumors by intrasplenic injection and evaluated total liver weights 26 days after therapy. Theoretically,