Tumor Dose–Response Relationship of [¹³¹I]MIBG Therapy in Patients with Neural Crest Tumors by Means of [¹²⁴I]MIBG PET

Abstract

[¹³¹I]Metaiodobenzylguanidine (MIBG) therapy in patients with neural crest tumors has demonstrated sustained control of catecholamine-associated hypertension and corresponding partial response. Details on how neural crest tumors respond to an absorbed dose delivered by [¹³¹I]MIBG-targeted therapies is insufficiently known. The primary aim of this retrospective study was to assess the tumor dose–response relationship by means of quantitative analysis of [¹²⁴I]MIBG PET data. Methods: The tumor dose–response relationship was studied in patients with advanced malignant pheochromocytoma, neuroblastoma, or paraganglioma receiving [¹³¹I]MIBG treatment, as well as pretherapeutic and follow-up [¹²⁴I]MIBG-based dosimetry. [¹²⁴I]MIBG PET imaging was performed around 4, 24, 48, and 120 h after injection. Lesion uptake was projected to [¹³¹I]MIBG for every time point, and respective time-integrated activity coefficients (TIACs) for [¹³¹I]MIBG were calculated and used for tumor-absorbed dose estimation. Functional response was denoted for decrease of maximal lesion uptake or TIAC by at least 30% in the follow-up examination. In a consecutive analysis, the predictive value of a single tumor-uptake assessment from PET imaging at 24 h after administration was investigated with respect to receiving the derived target dose. Results: In total, 46 lesions from 9 patients were available for dose–response analysis. The mean ± SD tumor-absorbed dose coefficient was 13.4 ± 15.4 Gy/GBq (median, 7.2 Gy/GBq; range, 1.1–64.7 Gy/GBq). A high correlation (−0.60, P < 0.001) was found between uptake decrease and tumor dose. In addition, a very high correlation (0.91, P < 0.001) was found between uptake and TIAC decrease. The estimated targeted tumor dose was 200 Gy, that is, the dose at which the response rate exceeded the 90% threshold. A single 24-h uptake assessment showed predictive value with respect to receiving the target dose. Conclusion: This study demonstrated a clear correlation between tumor-absorbed dose and functional response in [¹³¹I]MIBG therapy and proposes a target dose for response at the tumor level.