Abstract
We searched for methods that would enable prescriptions of the maximum tolerable doses of iodine-131 metaiodobenzylguanidine (MIBG) and iodine-125 MIBG in the treatment of patients with neuroblastoma. We correlated doses, defined in different ways, with subsequent platelet levels in treated patients to determine accurate predictors of the most frequent toxicity, thrombocytopenia. Nine patients with neuroblastoma were given 131I-MIBG (4.9–8.1 GBq or 132–220 mCi) and ten were given 125I-MIBG (8.3-30.0 GBq or 224–809 mCi) as initial treatments. These therapies were sufficiently varied that correlations could be made between indices of the doses and the subsequent toxicity as reflected in circulating platelet levels. Predictors of toxicity were: whole-body absorbed dose of radiation (cGy) calculated from pretherapy tracer doses of 131I-MIBG; GBq/kg of body weight; and GBq/m2 of body surface area. Toxicity was recorded as the nadir of the platelet level and platelet/pretherapeutic level (platelet ratio). For treatments with 131I-MIBG, the highest correlation was obtained between cGy and the logo10-transformed platelet ratio (r=−0.86), but comparison of GBq/m2 and the platelet nadir (r=−0.76) or the platelet ratio (r=−0.74) or the log10 − transformed platelet ratio (r=−0.73) gave comparable and statistically significant results. For treatments with 125I-MIBG, significant correlations were obtained between GBq/m2 and the platelet ratio (r=−0.81) or GBq/kg and the log10 −-transformed platelet ratio; the correlation between cGy and any toxicity index was low. Per administered GBq, 131I-MIBG was 2.6 times more potent than 125I-MIBG in causing a platelet ratio of 0.1. Thus, in predicting toxicity, therapeutic doses of 131I-MIBG expressed as GBq/m2 performed satisfactorily and almost as well as whole-body cGy, and treatment doses of 125I-MIBG expressed as GBq/m2 or GBq/kg performed satisfactorily and much better than whole-body cGy.
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References
Hoefnagel CA, Voûte PA, De Kraker J, Valdés Olmos RA. [131I]Metaiodobenzylguanidine therapy after conventional therapy for neuroblastoma. J Nucl Biol Med 1991;35: 202–206.
Hör G, Maul FD, Kornhuber B, Schwabe D, Hesse J, Manegold KH, Baüm RP, Gerein V. Outcome of [131I]metaiodobenzylguanidine therapy of neuroblastoma: seven years after. J Nucl Biol Med 1991;35: 207–215.
Klingebiel T, Feine U, Treuner J, Reuland P, Handgretinger R, Neithammer D. Treatment of neuroblastoma with [131I]metaiodobenzylguanidine: long-term results in 25 patients. J Nucl Biol Med 1991;35: 216–219.
Lumbroso J, Hartmann O, Schlumberger M. Therapeutic use of [131I]metaiodobenzylguanidine in neuroblastoma: a phase II study in 26 patients. J Nucl Biol Med 1991;35: 220–223.
Claudiani F, Garaventa A, Bertolazzi L, VillavecchiaGP, Cabria M, Scopinaro G, Bestagno M, Guerra P, Canevarollo N, Scielzo G, Lanino E, De Bernardi B. [131I]Metaiodobenzylguanidine therapy in advanced neuroblastoma. J Nucl Biol Med 1991;35: 224–227.
Troncone L, Rufini V, Riccardi R, Lasorella A, Mastrangelo R. The use of [131I]metaiodobenzylguanidine in the treatment of neuroblastoma after conventional therapy. J Nucl Biol Med 1991;35: 232–236.
Hutchinson RJ, Sisson JC, Miser JS, Zasadny KR, Normolle DP, Shulkin BL, Francis IR, Wieland DM, Shapiro B. Longterm results of [131I]metaiodobenzylguanidine treatment of refractory advanced neuroblastoma. J Nucl Biol Med 1991;35: 237–240.
Castellani MR, Rottoli L, Maffioli L, Massimino M, Gasparini M, Buraggi GL. Experience with palliative [131I]-metaiodobenzylguanidine therapy in advanced neuroblastoma. J Nucl Biol Med 1991;35: 241–243.
Matthay KK, Huberty JP, Hattner RS, Ablin AR, Engelstad BL, Zoger S, Hasegawa BH, Price D. Efficacy and safety of [131I]metaiodobenzylguanidine therapy for patients with refractory neuroblastoma. J Nucl Biol Med 1991;35: 244–247.
Hoefnagel CA, De Kraker J, Voute PA, Valdes Olmos RA. Preoperative [131I]metaiodobenzylguanidine therapy of neuroblastoma at diagnosis (“MIBG de novo”). J Nucl Biol Med 1991;35: 248–251.
Mastrangelo R, Lasorella A, Troncone L, Rufini V, Iavarone A, Riccardi R. [131I]Metaiodobenzylguanidine in neuroblastoma patients at diagnosis. J Nucl Biol Med 1991;35: 252–254.
Sisson JC, Hutchinson RJ, Shapiro B, Zasadny KR, Normolle D, Wieland DM, Wahl RL, Singer DA, Mallette SA, Mudgett EE. Iodine-125-MIBG to treat neuroblastoma: preliminary report. J Nucl Med 1990;31: 1479–1485.
Sisson JC, Shapiro B, Hutchinson RJ, Zasadny KR, Mallette S, Mudgett E, Wieland DM. Treatment of neuroblastoma with [125I]metaiodobenzylguanidine. J Nucl Biol Med 1991;35: 255–259.
Sisson JC, Hutchinson RJ, Carey JE, Shapiro B, Johnson JW, Mallette SA, Wieland DM. Toxicity from treatment of neuroblastoma with 131I-metaiodobenzylguanidine. Eur J Nucl Med 1988;14: 337–340.
Hutchinson RJ, Sisson JC, Shapiro B, Miser JS, Normolle D, Shulkin BL, Francis IR, Zasadny KR, Carey JE, Johnson JW, Mallette SA, Mudgette B. 131-I-Metaiodobenzylguanidine treatment in patients with refractory advanced neuroblastoma. Am J Clin Oncol 1992;15: 226–232.
Mangner TJ, Wu JL, Wieland DM. Solid phase exchange radioiodination of aryl iodides. Facilitation by amonium sulfate. J Org Chem 1982;47: 1484–1488.
Sisson JC, Shapiro B, Beierwaltes WH. Radiopharmaceutical treatment of malignant pheochromocytoma. J Nucl Med 1984;24: 197–206.
Lovinger R, Berman M. A revised schema for calculating the absorbed dose from biologically distributed radionuclides. MIRD Pamphlet No. 1, Revised. Society of Nuclear Medicine; 1976.
ICRU (1979). Methods of assessment of absorbed dose in clinical use of radionuclides. ICRU Report 32. Washington: International Commission on Radiation Units and Measurements, 1979.
Brownell WH, Ellett WH, Reddy AR. Absorbed fractions for photon dosimetry. MIRD Pamphlet No. 3. New York: The Society of Nuclear Medicine; 1968.
Fleiss J. Statistical methods for rates and proportions, 2nd edn. New York: John Wiley & Sons, 1981.
Corbett R, PinkertonR, Tait D, MellerS. [131I]Metaiodobenzylguanidine and high-dose chemotherapy with bone marrow rescue in advanced neuroblastoma. J Nucl Biol Med 1991;35: 228–231.
Sgouras G, Graham MC, Divgi CR, Larson SM, Scheinberg DA. Modeling and dosimetry of monoclonal antibody M195 (anti-CD33) in acute myelogenous leukemia. J Nucl Med 1993;34: 422–430.
Krenning EP, Bakker WH, Kooij PPM, Breeman WAP, Oei HY, de Jong M, Reubi JC, Visser TJ, Bruns C, Kwekkeboom DJ, Reijs AEM, van Hagen PM, Koper JW, Lamberts SWJ. Somatostatin receptor scintigraphy with indium-111-DTPA-Dphe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-tyr-3-octreotide. J Nucl Med 1992;33: 652–658.
Lashford LS, Moyes J, Ott R, Fielding S, Babich J, Mellors S, Gordon I, Evans K, Kemshead JT The biodistribution and pharmacokinetics of metaiodobenzylguanidine in childhood neuroblastoma. Eur J Nucl Med 1988;13: 574–577.
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Sisson, J.C., Shapiro, B., Hutchinson, R.J. et al. Predictors of toxicity in treating patients with neuroblastoma by radiolabeled metaiodobenzylguanidine. Eur J Nucl Med 21, 46–52 (1994). https://doi.org/10.1007/BF00182305
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DOI: https://doi.org/10.1007/BF00182305