Analysis of the principles of green chemistry in the radioiodination of metaiodobenzylguanidine compared to the principles already adopted for radiological protection

Antonio Pedro Junior; Eliene Bezerra Simão da Silva; Francisco José de Oliveira Ferreira; Rogerio Chaffin Nunes; Karine Rocha Ramos da Silva; Larissa Cunha Pinheiro; Fellipe Souza da Silva; Luciano Moreira Lima; Adriana Marques; Cintia Andrade Custódio; v Carvalheira

doi:10.15392/2319-0612.2026.2964

Autores/as

Antonio Pedro Junior IEN/CNEN , Nuclear Engineering Institute
Eliene Bezerra Simão da Silva Nuclear Engineering Institute
Francisco José de Oliveira Ferreira Nuclear Engineering Institute
Rogerio Chaffin Nunes Nuclear Engineering Institute
Karine Rocha Ramos da Silva Nuclear Engineering Institute
Larissa Cunha Pinheiro Radion, 21241-051, Rio de Janeiro, Rio de Janeiro, Brazil
Fellipe Souza da Silva Radion, 21241-051, Rio de Janeiro, Rio de Janeiro, Brazil
Luciano Moreira Lima Serviço Nacional de Aprendizagem Industrial , Serviço Nacional de Aprendizagem Industrial, 20550-010, Rio de Janeiro, Brazil
Adriana Marques National Water Agency , Agência Nacional de Águas, 70610-200, Distrito Federal, Brasília, Brazil
Cintia Andrade Custódio Nuclear Engineering Institute
v Carvalheira Nuclear Engineering Institute

DOI:

https://doi.org/10.15392/2319-0612.2026.2964

Palabras clave:

green chemistry, radiological protection, Radioiodination, Metaiodobenzylguanidine

Resumen

Environmental concerns have increasingly highlighted the importance of applying methodologies that prioritize safer waste treatments, the use of less toxic reagents, and milder synthesis conditions. In this context, radioiodinated metaiodobenzylguanidine (MIBG) stands out as a key radiopharmaceutical used in diagnostic scintigraphy and therapy of neural crest-derived tumors, such as pheochromocytoma and neuroblastoma, as well as in assessing sympathetic neuronal integrity after cardiac events. Halogenation reactions that avoid toxic reagents and hazardous conditions are essential for producing safe pharmaceutical compounds. Radioiodination, a specific type of halogenation, plays a critical role in the synthesis of radiopharmaceuticals—radioactive compounds formulated for diagnosing and treating human diseases. A major challenge in the production of radioiodinated MIBG is aligning the process with the principles of green chemistry, emphasizing the use of harmless substances and minimizing their quantities, while also meeting stringent nuclear, radiological protection, and pharmaceutical regulations. However, green chemistry considerations are often neglected in this process. This study quantitatively assesses the application of green chemistry principles to existing radioiodination methods for MIBG. The degree of compliance with each principle was expressed as a percentage. Additionally, a qualitative analysis was conducted to explore the alignment between green chemistry and radiological protection principles. Green chemistry is guided by twelve principles: Prevention, Atom Economy, Less Hazardous Chemical Syntheses, Designing Safer Chemicals, Safer Solvents and Auxiliaries, Energy Efficiency, Renewable Feedstocks, Reducing Derivatives, Catalysis, Design for Degradation, Real-Time Analysis for Pollution Prevention, and Inherently Safer Chemistry for Accident Prevention. This work examines how each principle applies to MIBG radioiodination, with some aspects also discussed in the broader context of radiopharmaceutical production. While radioiodinated MIBG complies fully with pharmaceutical requirements in its final medicinal formulation, its production currently incorporates about 68% of the green chemistry principles. As radiopharmaceutical production moves forward, greater attention should be given to eco-friendly practices. Investing time and resources into adopting green principles for MIBG radioiodination is a logical next step. This radiopharmaceutical holds well-established clinical importance, and future advances in its production should embrace sustainable, environmentally conscious methodologies.

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