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Targeting of meta‐iodobenzylguanidine to SK‐N‐SH human neuroblastoma xenografts: Tissue distribution, metabolism and therapeutic efficacy
Author(s) -
Rutgers Marja,
Buitenhuis Corine K.M.,
Hoefnagel Cees A.,
Voûte P.A.,
Smets Lou A.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20000801)87:3<412::aid-ijc16>3.0.co;2-x
Subject(s) - neuroblastoma , medicine , biodistribution , radiation therapy , in vivo , nuclear medicine , scintigraphy , dosimetry , cancer research , absorbed dose , therapeutic index , pharmacology , biology , cell culture , drug , genetics , microbiology and biotechnology
The clinical results of [ 131 I]meta‐iodobenzylguanidine (MIBG)–targeted radiotherapy in neuroblastoma patients is highly variable. To assess the therapeutic potential of [ 131 I]MIBG, we used the SK‐N‐SH human neuroblastoma, xenografted in nude mice. The model was first characterized for basic parameters of MIBG handling in the host species. This demonstrated the presence of both strain‐ and nu/nu mutation–related differences in [ 131 I]MIBG biodistribution. Fecal and urinary clearance rates of [ 131 I]MIBG in mice roughly resemble those in humans, but mice metabolize MIBG more extensively. In both species, enzymatic deiodination in vivo was not an important metabolic route. Therapy with increasing [ 131 I]MIBG doses (25–92 MBq) given as single i.v. injections resulted in proportionally increasing specific growth delay values (tumor regrowth delay/doubling time) of 1 to 5. Using gamma‐camera scintigraphy for non‐invasive dosimetry, the corresponding calculated absorbed tumor radiation doses ranged from 2 to 11 Gy. We also compared the therapeutic effects of a single [ 131 I]MIBG administration with those resulting from a more protracted exposure by fractionating the dose in 2 to 6 injections or with high dose rate external‐beam irradiation. No therapeutic advantage of a fractionated schedule was observed, and 5.5 Gy delivered by low dose‐rate [ 131 I]MIBG endo‐irradiation was equi‐effective with 5.0 Gy X‐rays. The SK‐N‐SH neuroblastoma xenograft model thus appears suitable to evaluate possible treatment improvements to reach full potential of MIBG radiotherapy. Int. J. Cancer 87:412–422, 2000. © 2000 Wiley‐Liss, Inc.