Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases.

Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents.

The role of electron-emitting radiopharmaceuticals in the palliative treatment of metastatic bone pain and for radiosynovectomy: applications of conversion electron emitter Tin-117m

A variety of radionuclides continue to be investigated and/or clinically used for different therapeutic applications in nuclear medicine. The choice of a particular radionuclide with regard to appropriate emissions, linear energy transfer (LET), and physical half-life, etc., is dictated to a large extent by the character of the disease (e.g., solid tumor or metastatic disease), and by the carrier to selectively transport the radionuclide to the desired site. An impressive body of information has appeared in the recent literature that addresses many of these considerations. This article summarizes and discusses the role of high-LET electron emitters and their advantage in the treatment of cancer or for other disorders in specific situations. Areas such as bone pain palliation, bone malignancy therapy, and radiation synovectomy are covered in greater detail. Projections are made as to the future directions and progress in these areas. A discussion of the various issues related to the selection criteria that are useful for choosing the appropriate radionuclide for a particular application is included. Use of high-LET electron emitters is discussed in greater detail, with particular emphasis on the use of conversion electron emitter tin-117m for various therapeutic applications.

Uma variedade de radionuclídeos continua a ser investigada e/ou clinicamente utilizada para diferentes aplicações terapêuticas em medicina nuclear. A escolha de um radionuclídeo, considerando-se sua emissão apropriada, transferência linear de energia (LET) e meia-vida física é determinada na maior parte pelo caráter da doença (p.ex., tumor sólido ou doença metastática), e pelo carreador que transporta o radionuclídeo seletivamente para o sítio desejado. Um notável conjunto de informações voltadas para essas considerações tem aparecido na literatura recente. Esse trabalho resume e discute o papel de emissores de elétrons de alta-LET e sua vantagem no tratamento do câncer ou para outras doenças em situações específicas. Abordagens relacionadas com o alívio da dor óssea, a terapia da doença óssea e a sinovectomia por radiação são apresentadas detalhadamente. Projeções para o futuro e os progressos nessas áreas são indicadas. Uma profunda discussão relacionada aos critérios de seleção que são úteis para escolher o radionuclídeo apropriado para que uma aplicação particular seja incluída. O uso de emissores de elétrons de alta-LET é discutido em grande detalhe, com particular ênfase no uso do estanho-117m, um emissor de elétron de conversão, para várias aplicações terapêuticas.