What are the potential uses and applications of Terbium (a radioisotope) in Nuclear Medicine, particularly for cancer treatment and imaging?

Terbium as a Novel Radioisotope in Nuclear Medicine

Overview and Theranostic Potential

Terbium represents a unique family of four medically-relevant radioisotopes (149Tb, 152Tb, 155Tb, and 161Tb) that enable true theranostic applications through their identical chemical properties but distinct decay characteristics, allowing matched-pair imaging and therapy with the same radiopharmaceutical. 1, 2

The terbium quartet spans the entire spectrum of nuclear medicine applications:

• 149Tb (T1/2 = 4.1 h): α-particle therapy with concurrent PET imaging capability 1, 2
• 152Tb (T1/2 = 17.5 h): PET imaging for pre-therapeutic dosimetry 1, 2
• 155Tb (T1/2 = 5.32 d): SPECT imaging for treatment planning 1, 2
• 161Tb (T1/2 = 6.96 d): β-/Auger electron therapy as a potential alternative to 177Lu 1, 3

Clinical Applications

Therapeutic Applications

161Tb is the most clinically advanced therapeutic terbium isotope, offering combined β- and Auger electron therapy that has demonstrated superior efficacy compared to 177Lu in preclinical studies. 1, 2

• The co-emission of Auger electrons alongside medium-energy β-particles provides enhanced therapeutic potential for targeted radionuclide therapy, particularly in cancer treatment 1, 2
• The 6.96-day half-life is comparable to 177Lu, making it suitable for peptide receptor radionuclide therapy and other targeted applications 3
• 149Tb enables targeted α-therapy with the unique advantage of concurrent PET imaging for real-time treatment monitoring 1, 2

Diagnostic Applications

152Tb and 155Tb serve as diagnostic counterparts for pre-therapeutic imaging and dosimetry calculations using chemically-identical radiopharmaceuticals. 1, 2

• 152Tb has been tested in proof-of-concept clinical studies (as 152Tb-DOTATOC) in patients, representing the first terbium isotope used clinically 2
• 155Tb provides SPECT imaging capability for dosimetry purposes prior to therapeutic radionuclide administration 1, 2
• Both isotopes enable accurate prediction of therapeutic dose distribution using the same targeting vector that will be used for therapy 1, 2

Production and Availability Challenges

Current Production Status

161Tb and 155Tb are the most promising isotopes for large-scale clinical translation, with reactor-based neutron capture representing the primary production route. 1, 2

• Reactor production via neutron capture reactions provides the most viable pathway for clinical-scale quantities 2
• Alternative production routes, such as the 160Gd(d,n)161Tb reaction, achieve only 86% radionuclidic purity and are not suitable for medical applications due to 160Tb contamination 4
• 152Tb and 149Tb production remains more challenging and is currently limited to research quantities 2

Quality Control Considerations

Accurate half-life determination is critical for decay-corrected activity calculations, with recent measurements establishing the 161Tb half-life at 6.9637(29) days—approximately 1% longer than previously evaluated. 3

• This revised half-life value significantly impacts dosimetry calculations and must be incorporated into clinical protocols 3
• The uncertainty in half-life determination contributes substantially to overall activity measurement uncertainty 3

Radiopharmaceutical Development

Chelator Requirements

p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA, and p-SCN-3p-C-NETA are suitable bifunctional chelators for terbium-based radiopharmaceuticals, enabling high-yield radiolabeling under mild conditions (40°C) that preserve heat-sensitive biomolecules. 5

• These chelators achieve >98% radiochemical yields at 40°C, preventing thermal degradation of antibodies and peptides 5
• In vivo stability studies demonstrate negligible bone uptake over 7 days with DOTA, DOTA-GA, and NETA variants, indicating stable chelation 5
• p-SCN-Bn-CHX-A"-DTPA shows increasing bone accumulation over time, suggesting in vivo instability and is not recommended 5

Pharmacokinetic Advantages

The identical chemical properties of all four terbium isotopes ensure that radiopharmaceuticals maintain the same biodistribution, pharmacokinetics, and targeting characteristics regardless of which isotope is used. 1, 2

• This enables seamless transition from diagnostic imaging (152Tb or 155Tb) to therapy (161Tb or 149Tb) without changing the targeting vector 1, 2
• Dosimetry calculations from diagnostic scans directly predict therapeutic dose distribution 1, 2

Current Clinical Status and Future Prospects

Terbium radioisotopes remain primarily in preclinical and early clinical development, with 152Tb having achieved proof-of-concept clinical testing and 161Tb showing the most promise for near-term therapeutic applications. 1, 2

Implementation Barriers

• Limited production capacity restricts availability for widespread clinical use 2
• Standardized production and quality control protocols require further development 1
• Regulatory pathways for novel radioisotopes need establishment 1
• Cost-effectiveness compared to established radioisotopes (177Lu, 225Ac) requires demonstration 2

Integration with Existing Nuclear Medicine Infrastructure

Terbium-based radiopharmaceuticals can be integrated into existing nuclear medicine facilities without requiring specialized equipment beyond standard PET/SPECT cameras and radiation safety protocols. 6

• Gamma camera systems and PET scanners currently used for other radioisotopes are compatible with terbium imaging 6
• Radiation protection measures follow established principles for handling therapeutic radioisotopes 6
• Quality assurance programs and accreditation standards apply similarly to terbium-based procedures 6