Improved effect of 131I-MIBG treatment by predosing with non-radiolabeled MIBG in carcinoid patients, and studies in xenografted mice

Background: I-131-meta-iodobenzylguanidine (MIBG) has been used with success for the palliation of metastatic carcinoid. To qualify more patients for this treatment, we evaluated the effect of predosing with non-radiolabeled MIBG on I-131-MIBG tumour targeting in carcinoid patients and in mice with BON human carcinoid xenografts. Patients and methods: Ten carcinoid patients with a faint tumour imaging on a diagnostic I-131-MIBG scan (1 mCi = 37 MBq, 5 mg MIBG) received non-radiolabeled MIBG prior to a second scintigraphy. In case of improved tumour targeting patients were treated with 200 mCi (7.4 GBq) I-131-MIBG following a pharmacological predose of 20-40 mg/m(2) MIBG. Results: In six patients, highly increased `tumour/non-tumour' ratios were seen due to reduced levels in normal tissues and increased tumour accumulation. The combined treatment applied in five patients, considerably improved symptoms in all (duration 6-12 months), accompanied by biochemical response in three. In BON carcinoid xenografted mice, MIBG was injected intraperitoneally followed by intravenous I-125-MIBG with similar findings: increased `tumour/non-tumour' radioactivity ratios by 1.5-3-fold. Conclusion: Predosing with non-radiolabeled MIBG resulted in improved I-131-MIBG tumour targeting, prolonged palliation and encouragingly often biochemical responses in carcinoid.