123I-Iobenguane (MIBG)

Description

¹²³I-Iobenguane, also known as ¹²³I-Metaiodobenzylguanidine (¹²³I-MIBG), is a radiopharmaceutical diagnostic agent used for the detection of primary or metastatic pheochromocytoma and neuroblastoma. Marketed under names such as Adreview™ and MIP-120, it is a crucial tool in nuclear medicine imaging, especially in oncology and cardiology. Originally approved in various countries, GE Healthcare later pursued and obtained marketing authorization (MA) for this agent in the United States. The U.S. Food and Drug Administration (FDA) approved Adreview™ in March 2013 for imaging of sympathetic innervation in the heart, thereby expanding its clinical utility beyond oncology.

Clinical Applications

¹²³I-Iobenguane has a range of diagnostic applications. Primarily, it is employed to identify and localize pheochromocytomas and neuroblastomas, which are tumors of the adrenal gland and nervous system, respectively. Its role in cardiac imaging is also significant. It is used for the scintigraphic assessment of sympathetic innervation in the myocardium of patients with heart failure. This imaging can help stratify patients by identifying those with lower one- and two-year mortality risks, providing critical insights for patient management.

The FDA’s 2013 approval of ¹²³I-Iobenguane for cardiac imaging reflected its growing importance in cardiology, a trend mirrored in Japan where similar regulatory approval was granted. MIP also explored its potential for other imaging applications under the name MIP-120. Although it was proposed for imaging neuroendocrine tumors (NETs), clinical comparisons revealed that ¹²³I-MIBG was less sensitive than ^99mTc-Octreotide. However, ¹²³I-MIBG retained comparable sensitivity to Octreotide for detecting pheochromocytomas, reinforcing its relevance for this specific indication.

Availability

The regulatory landscape for ¹²³I-Iobenguane reveals a patchwork of approvals across different regions. GE Healthcare obtained the first FDA marketing authorization for this tracer in September 2008 under the brand name Adreview™. In the European Union (EU), the MA was secured earlier, in February 2005. While these regulatory milestones marked GE Healthcare’s formal entry into the market, other forms of ¹²³I-MIBG had already been available in the EU and Japan for years.

Generic versions of ¹²³I-MIBG have since become widely accessible. Key suppliers include Fuji-Film, which markets MyoMIBG-I123 and obtained marketing authorization in Japan in 2011 for the diagnosis of melanocytoma. IBA Molecular produced a version known as IK-4, which had EU MA in 2002 but is no longer available. Mallinckrodt (Curium) and Monrol are also notable suppliers, with Monrol’s version marketed as MON.MIBG ¹²³I-Diagnostic. Pricing for Adreview™ in the U.S. reflects the high cost of radiopharmaceuticals, with the average price per diagnostic dose approximating USD 6,700.

Market Competition

The market for ¹²³I-Iobenguane has grown increasingly competitive, with several generic versions available. Companies such as Fuji-Film, Monrol, and Curium have diversified the supply landscape. However, for a relatively niche indication, this crowded market poses challenges for manufacturers looking to maintain profitability.

Competition is not limited to generic ¹²³I-MIBG. Other imaging agents have emerged as alternatives. For example, the ¹³¹I-labeled analogue (¹³¹I-MIBG) is used for the same indications but at lower doses, especially in diagnostic applications. In Japan, ¹²³I-MIBG faces direct competition from ¹²³I-BMIPP, another cardiac imaging agent. Outside Japan, this competition is less relevant as ¹²³I-BMIPP is not widely authorized.

Further competition arises from ¹⁸F-FDOPA, a PET imaging agent that has demonstrated higher sensitivity than ¹²³I-MIBG for certain indications. However, ¹⁸F-FDOPA’s availability remains limited due to production challenges and the need for specialized PET centers. As a result, clinicians who do not have access to PET imaging may continue to rely on ¹²³I-MIBG for neuroblastoma and pheochromocytoma imaging.

Key Insights and Industry Observations

¹²³I-Iobenguane exemplifies the varied pathways through which radiopharmaceutical tracers can evolve. While initially focused on oncology indications like pheochromocytoma and neuroblastoma, companies expanded its use into cardiology, thereby broadening its market potential. Regulatory differences between regions have also influenced the development and commercialization strategies for ¹²³I-MIBG.

One key distinction is the presence of generics. In the EU, multiple generic suppliers exist, while in the U.S., Adreview™ remains the primary product. This disparity is partly due to the lack of intellectual property (IP) protection for ¹²³I-MIBG, which allowed for earlier entry of generic versions in Europe and Japan. GE Healthcare’s strategy to maintain market dominance involved securing orphan drug designation in the U.S. and developing new indications such as cardiac imaging.

However, access to ¹²³I-MIBG has been limited due to the high cost and logistical challenges associated with ¹²³I production. The advent of PET technology, offering tracers like ¹⁸F-FDOPA, has further complicated the market. Clinicians have expressed frustration over the limited availability of ¹⁸F-FDOPA, particularly since it outperforms ¹²³I-MIBG in sensitivity for certain neuroendocrine tumors. As a result, clinicians resort to ¹²³I-MIBG imaging only when PET tracers are inaccessible.

Conclusion

¹²³I-Iobenguane (MIBG) has played a pivotal role in the detection and diagnosis of pheochromocytoma, neuroblastoma, and cardiac sympathetic innervation. Despite competition from PET tracers and other alternatives, it remains a key diagnostic agent due to its accessibility and established clinical efficacy. Regulatory and commercial strategies have significantly influenced its availability and pricing, with regional differences in the presence of generics, the scope of approvals, and the evolution of new clinical indications. As newer, more sensitive tracers like ¹⁸F-FDOPA emerge, the role of ¹²³I-MIBG may diminish, but for now, it remains an essential tool in specific diagnostic workflows.