188Re-Rhenium Etidronate (HEDP)

Description

¹⁸⁸Re-Rhenium Etidronate, also known by its various designations such as ¹⁸⁶Re-HEDP, hydroxyethylidene diphosphonate, ¹⁸⁶Re-Etidronate, ¹⁸⁸Re-Hydroxyethanediphosphonate, and ¹⁸⁸Re-REK-1, is a radiopharmaceutical agent with significant applications in medical treatments. It is commercially available in India through BRIT/BARC for radiosynovectomy procedures.

This compound is also being actively developed as a therapeutic agent for treating bone metastases. In China, Shanghai YiTai Pharmaceutical Technology Company Ltd. is spearheading its development with support from IRE-Elit, which provides the necessary ¹⁸⁸W/¹⁸⁸Re generator. Similarly, in Iran, ¹⁸⁸Re-HEDP is accessible for research purposes through Pars Isotope.

Clinical Applications

¹⁸⁸Re-HEDP is primarily indicated for radiosynovectomy, leveraging its high affinity for hydroxyapatite crystals that constitute the inorganic structure of bone tissue. This characteristic makes it particularly effective for treating bone metastases in both primary and metastatic bone tumors.

• Dosage: The typical dose per patient ranges from 80 to 100 mCi.
• Cost Efficiency: Compared to its counterpart, ¹⁸⁶Re-HEDP, ¹⁸⁸Re-HEDP offers a cost advantage. The shorter half-life of ¹⁸⁸Re also facilitates dose fractionation, making it a practical option.
• Efficacy: The maximum tolerated dose for ¹⁸⁸Re is higher than that of ¹⁸⁶Re, further enhancing its therapeutic potential.

Notably, reviews published in 2018 underscore its efficacy and potential benefits in clinical applications.

Additional Development

¹⁸⁸Re-Rhenium Etidronate is currently in Phase III clinical trials in China. However, detailed information about these trials from YiTai is limited.

Key Findings from Previous Research:

• A 2009 clinical trial conducted in Germany demonstrated a remarkable improvement in post-treatment overall survival for patients receiving multiple injections of bone-targeted therapy. Survival increased from 4.5 months (single injection) to 15.7 months (multiple injections), indicating that ¹⁸⁸Re-HEDP is not solely a palliative treatment but also extends patient survival significantly.
• Initial clinical data highlighted that repeated treatments with ¹⁸⁸Re-HEDP yielded better outcomes compared to single applications, emphasizing its potential for enhancing overall survival.

Ongoing Research: In 2018, a large-scale clinical trial involving 400 patients was initiated at VU University Medical Center in Amsterdam, Netherlands. This trial aims to compare ¹⁸⁸Re-HEDP with ²²³Ra-Xofigo in treating castration-resistant prostate cancer with bone metastases. The primary endpoint of this study is overall survival. Preliminary results were anticipated by 2022, with the final outcomes expected by 2024.

Availability

Currently, ¹⁸⁸Re-HEDP is available in India through BRIT (REK-1) but is limited to radiosynovectomy applications.

Competition

In the realm of radiosynovectomy, ¹⁸⁸Re-HEDP faces competition from other locally available drugs such as:

• ¹⁶⁹Er-Erbium Citrate
• ⁹⁰Y-Yttrium Colloids
• ¹⁸⁶Re-Rhenium Sulfide

Comments

The accessibility and broader development of ¹⁸⁸Re-HEDP are contingent upon securing approval for at least one ¹⁸⁸W/¹⁸⁸Re generator. Currently, these generators lack approval, and the availability of the drug in India is subject to local authorizations. BARC is reportedly working on developing its own generator, which could potentially address this limitation.

Considerations for Development:

• Expanding the use of ¹⁸⁸Re-HEDP beyond India for radiosynovectomy applications will require comprehensive drug development and approval processes.
• Given the competitive environment, pursuing further development at this stage may not be immediately practical. Emerging proprietary drugs, such as those labeled with ^117mSn, represent potential alternatives.

Broader Applications and Market Position

¹⁸⁸Re-HEDP stands out as the first bone tumor-targeting agent specifically developed for therapeutic use. However, it must contend with established market competitors in bone pain palliation, including:

• ³²P
• ⁸⁹Sr-Chloride
• ¹⁵³Sm-EDTMP
• ²²³Ra-Xofigo (recently launched)

If ¹⁸⁸Re-HEDP demonstrates superior efficacy in overall survival (OS) alongside pain palliation, it could emerge as a significant competitor to Xofigo, especially in developing countries where its lower cost could offer a competitive edge.

Technical Insights

One notable finding in targeting bone tissue with ¹⁸⁸Re is the demonstrated superiority of carrier-added ¹⁸⁸Re formulations. Unlike the no-carrier-added (NCA) form, carrier-added ¹⁸⁸Re facilitates the formation of active species with rhenium-rhenium bonds, which are essential for therapeutic efficacy. This makes ¹⁸⁸Re-HEDP one of the rare instances where a carrier-added formulation is preferable and more effective.