123I-Iodofiltic Acid (BMIPP)

Description

¹²³I-Iodofiltic acid, also known as ¹²³I-BMIPP (15-(4-iodophenyl)-3-methylpentadecanoic acid), is a myocardial perfusion imaging (MPI) agent primarily used in Japan. Since its approval in 1993, ¹²³I-BMIPP has played a crucial role in cardiac imaging, marketed by Nihon Medi-Physics under the name Cardiodine™. Outside Japan, development efforts were led by Molecular Insight Pharmaceuticals (MIP) under the brand name Zemiva^®, though these efforts have since been paused. ¹²³I-BMIPP’s unique mechanism, as a methyl fatty acid analog, allows it to be taken up and retained by myocardial cells, offering distinct imaging advantages over conventional tracers.

Clinical Applications

¹²³I-BMIPP is widely utilized as a SPECT cardiac imaging agent in Japan, where it is employed in approximately 20% of cardiology studies. Unlike more common tracers such as ²⁰¹Tl-Thallium Chloride, ^99mTc-Sestamibi, or ^99mTc-Tetrofosmin, ¹²³I-BMIPP offers unique clinical benefits. By allowing for the imaging of ischemic areas shortly after an event, it facilitates early and effective intervention.

A key advantage of ¹²³I-BMIPP is its ability to image myocardial ischemia without the need for exercise or pharmacologic stress. This makes it especially valuable for patients with contraindications for stress testing. Furthermore, it has the capability to assess metabolic changes in ischemic myocardium, with the tracer remaining in myocardial cells for extended periods compared to faster-clearing 99mTc agents. The standard dosage per patient is around 3 mCi, and imaging can be conducted shortly after tracer injection.

Stage of Development

The development of ¹²³I-BMIPP in the U.S. focused on its potential role in emergency departments for the rapid diagnosis of myocardial ischemia or heart attack. Its extended myocardial retention was seen as a major advantage, providing a wider imaging window compared to ^99mTc-labeled agents. MIP initiated clinical trials for Zemiva^®, with a Phase II study involving 600 patients in the U.S. completed in 2009. However, further development in the U.S. stalled in 2013, primarily due to logistical and cost-related challenges.

While Japan continues to use ¹²³I-BMIPP routinely for cardiac imaging, no comparable regulatory approval or commercial activity has been achieved in other regions. The discontinuation of development in the U.S. was largely driven by issues with the production, distribution, and logistical feasibility of ¹²³I-labeled tracers.

Availability

¹²³I-BMIPP is commercially available in Japan from Nihon Medi-Physics under the trade name Cardiodine™. Outside Japan, the production and availability of ¹²³I-BMIPP are more limited. Doses must be produced on a per-patient basis at local radiopharmacies, significantly increasing costs and operational complexity.

Market Competition

The market for myocardial perfusion imaging (MPI) is dominated by ^99mTc-labeled agents, such as ^99mTc-Sestamibi and ^99mTc-Tetrofosmin. These agents are well-established globally, benefiting from lower production costs, wider distribution, and simpler logistics. By comparison, ¹²³I-BMIPP faces several competitive disadvantages. While ¹²³I-BMIPP’s lack of reliance on stress testing and its extended myocardial retention offer clinical benefits, these features have not been sufficient to overcome its higher cost and logistical challenges.

Unlike ^99mTc-based tracers, which are widely available and affordable (often under EUR 100 or USD 110 per dose), the price of ¹²³I-BMIPP is significantly higher. In the U.S., estimates suggest that ¹²³I-BMIPP would need to be priced at around EUR 1,000 (USD 1,100) per dose to cover production and logistics costs. This pricing disparity makes it difficult for ¹²³I-BMIPP to compete with ^99mTc agents, which are more accessible and economically viable.

Comments and Industry Insights

One of the critical barriers to the widespread adoption of ¹²³I-BMIPP in the U.S. is the logistical complexity of handling ¹²³I. Unlike Japan, where the distribution of ¹²³I-labeled tracers is supported by a network of large-scale cyclotrons, the U.S. lacks a similar infrastructure. Manufacturing and distributing ¹²³I-tracers across the U.S. would require significant investment, estimated at EUR 30-40 million (USD 40-50 million), to establish GMP-grade production and distribution capacity.

Furthermore, due to the short half-life of ¹²³I, maintaining supply across large geographical areas requires doses to be prepared at local production sites. For hospital emergency departments to benefit from ¹²³I-BMIPP’s imaging potential, the tracer must be available on-site within 1 to 2 hours of patient presentation. This is logistically feasible with ^99mTc-labeled agents but far more challenging with ¹²³I-labeled products. Possible solutions, such as pre-manufacturing and storing doses on-site, are costly and require daily production of two batches to avoid dose expiration. These production costs must be absorbed into the total cost of the tracer, further driving up prices and creating resistance from cardiologists and healthcare providers.

Given the substantial logistical hurdles and high production costs, it is unlikely that ¹²³I-BMIPP will gain a strong foothold in global MPI markets. While its clinical benefits are recognized, particularly for patients unable to undergo stress testing, the economic and operational burdens associated with its use are significant. This explains why ¹²³I-BMIPP remains a niche product, with its use largely confined to Japan. Efforts to reintroduce the tracer in the U.S. or other regions would require major investments in production infrastructure and a strategy to justify the higher cost of the tracer relative to more established ^99mTc-labeled alternatives.