1. INTRODUCTION

Radiopharmaceuticals, along with imaging instrumentation, are the pillars that support the edifice of clinical nuclear medicine and the former is the major driver enabling investigations of molecular phenomena for better understanding of human disease and developing effective treatments. The growth of nuclear medicine has been intimately linked to availability of new radioisotopes and the discovery of new radiopharmaceuticals. The field of radiopharmaceuticals has witnessed continuous evolution thanks to the immense contributions of scientists from diverse disciplines such as radiochemistry, inorganic chemistry, organic chemistry, biochemistry, physiology and pharmacology. Several milestones can be cited in the trajectory of this growth, which include continuing development of a plethora of ^99mTc radiopharmaceuticals, automated synthesis of ¹⁸F labelled compounds, labelled peptides for accurate mapping of metastasis and the advances in radionuclide therapy. The International Symposium on Trends in Radiopharmaceuticals, ISTR-2005, under the auspices of International Atomic Energy Agency, will provide scientists and professionals working in the field of radiopharmaceuticals and related sciences an opportunity to review the exciting developments in the field. The International Atomic Energy Agency has been organizing such Symposia on Radiopharmaceuticals since 1973 and the last one was held in Lisbon, Portugal, in 1998.

2. BACKGROUND

The field of technetium radiopharmaceutical chemistry has grown at an accelerated pace in the last decade thanks to new chemistries such as the nitrido, carbonyl and hynic together with the synthesis of several novel ligands fitting to these chemistries. These pioneering studies are making the anthropogenic element technetium the most explored metal ion for its complexation behaviour. Several new ^99mTc radiopharmaceuticals continue to be developed, aiming for greater efficacy in exploring biochemistry in vivo and introducing accuracy of diagnosis of metastatic cancer to lead to greater objectivity in medical decisions.

The cyclotron, originally developed for nuclear physics research, has been simplified for the benefit of increasing medical applications, being the ideal source for many short-lived, neutron-deficient radioisotopes, and is today a versatile tool in the hands of the radiopharmaceutical scientists. There is a significant growth in the installation of new cyclotrons to cater to the production of radionuclides for medical applications and interesting developments are taking place through the development of better cyclotron targetry, radiochemical processing methods and automated chemistry modules. The short half-life of most of these radioisotopes makes it essential that the process be automated, starting from irradiation all the way to the final dispensing stage, such that the final radiopharmaceutical formulation is compliant with the codes of Good Manufacturing Practices (cGMP). There is a continuing need to evolve appropriate guidelines of cGMP for radiopharmaceuticals, due to the conflicting requirements for handling radioactivity and formulating products for intravenous administration.

The most spectacular development is undoubtedly the advances in the synthesis of ¹⁸F labelled fluoro deoxy glucose (FDG), opening a new avenue in nuclear medicine, namely the regular clinical use of positron emission tomography (PET). Initially developed for studying glucose metabolism in vivo, especially to map the regional cerebral functions under various conditions, today ¹⁸FDG is the most useful clinical PET tracer for the detection, staging, treatment planning and management of cancer. Research into other ¹⁸F labelled molecules, including peptides and agents for tracking gene therapy, has resulted in several new radiopharmaceuticals. The quest for newer and more specific ¹⁸F labelled radiopharmaceuticals keeps PET chemists busy the world over. The work on other short-lived PET radionuclides, mainly ¹¹C and to a lesser extent ¹⁵O, is also continuing, despite the logistical problems due to their short half-lives.

The radiohalogens play a pivotal role in the growth of nuclear medicine by the continued use of iodine isotopes such as ¹³¹I, ¹²³I, ¹²⁴I for diagnosis and therapy. Strategies to increase the availability of ¹²³I products are important for clinical nuclear medicine practices. The bromine and astatine isotopes are being vigorously explored for establishing their utility in clinical nuclear medicine. The use of the short-lived SPECT isotopes such as ²⁰¹Tl, ¹¹¹In and ⁶⁷Ga is continuing to grow for diagnostic imaging starting from myocardial studies to tumour and infection imaging.

One of the challenges in the coming years will be to take advantage of the potentials of radiolabelled peptides to formulate clinically useful radiopharmaceuticals. Peptide receptors have been found to represent excellent targets for in vivo cancer diagnosis and therapy.

Recent in vitro studies have shown that many cancers can over-express not just one but several peptide receptors concomitantly. This presents a basis for starting and/or optimizing the in vivo targeting of tumours by selecting suitable radiopeptides initially for tumour diagnosis and later with appropriate radionuclides for therapy as well.

In addition, nuclear medicine is being transformed from a non-invasive diagnostic methodology to a powerful therapeutic modality. There continues to be growth in the use of ¹³¹I for cost effective treatment of hyperthyroidism and metastatic thyroid cancer. Radiopharmaceuticals such as ⁸⁹SrCl₂, ¹⁵³Sm-EDTMP and ¹⁸⁶Re-HEDP are increasingly used in many centres as cost effective bone pain palliative agents. The use of ¹³¹I-mIBG and ¹³¹I/¹⁸⁸Re labelled lipiodol continues to attract attention, with growing medical interest in neuro-endocrine tumours and extensive difficulties with liver cancer, respectively. There is great excitement in the prospect of very specific therapeutic targeting with radiolabelled peptides with radionuclides such as ⁹⁰Y, ^186/188Re and ¹⁷⁷Lu. Generator produced radionuclides offer a new dimension to availability of therapeutic radiopharmaceuticals. Non-conventional applications include synoviorthesis using radiopharmaceuticals labelled with beta particle emitting radioisotopes to improve the quality of life of patients suffering from rheumatoid arthritis. Intravascular radionuclide therapy (IVRNT) for prevention of arterial restenosis post-percutaneous transluminal coronary angioplasty (PTCA) is an attractive alternative to drug eluting stents.

While surgery remains the most effective method for managing cancer, radiopharmaceuticals play a useful role there too, being the preferred markers for identifying metastatic lymph nodes and helping surgeons to achieve better precision in tumour mass excision. Accordingly, a new modality, radioguided surgery (RIGS), is emerging for use in the operating theatre.

The major constituent of a radiopharmaceutical is the radionuclide and the search for new radionuclides to improve the availability of diagnostic and therapeutic radiopharmaceuticals is continuing. Several metallic isotopes such as ^60/61/62Cu, ⁶⁸Ga, ⁸⁶Y and ⁹⁴Tc are emerging for PET studies. In view of the promising advances in targeted therapy for cancer management, the need for therapeutic radioisotopes is expected to grow manifold. Internalized targeted therapy can be highly specific in its ability to deliver radiation dose to the tumour and hence, when the potential of targeted therapy is fully realized, the demand for radioisotopes for this modality will be huge. Keeping this in mind, radionuclides that can be produced in abundant quantity are being explored. ⁹⁰Y, the daughter of the long-lived fission product ⁹⁰Sr, and ¹⁷⁷Lu, which can be produced by (n,ã) activation of ¹⁷⁶Lu, are the two isotopes which can meet such large demands. Efforts are being made to develop new production routes and radiochemical processing methods, as well as radionuclide generator technologies, to effectively bridge the gap between demand and supply.

A review of the radiopharmaceuticals field would be incomplete without a discussion about centralized radiopharmacy practices. There is a continuing need to formulate radiopharmaceuticals cost effectively and to a high standard of consistent quality. There is need for improvements in the systems for dispensing of PET and therapeutic radiopharmaceuticals. This symposium will focus on practices and facilities for greater pharmaceutical safety and better radiation hygiene.

The exciting developments in all the above areas in the radiopharmaceuticals field are contributing to transforming nuclear medicine to a preferred modality for diagnosis and therapy of many diseases not only in developed countries but also in most developing nations.

3. TOPICS

The symposium will cover developments in the entire spectrum of radiopharmaceuticals chemistry, including radionuclide production, radiochemical processing, manufacturing and quality control of radiopharmaceuticals, latest advances in radiopharmaceuticals research, GMP and regulatory aspects, etc.

The IAEA welcomes high quality contributions on the following topics.

Radionuclide production and synthesis of radiopharmaceuticals

Novel technetium chemistry and radiopharmaceuticals

Flourine-18 and iodine-123 based radiopharmaceuticals and automation of synthesis

Other radiohalogens and metallic nuclides for PET

Carbon-11 radiopharmaceuticals and other short-lived PET tracers

Therapeutic radiopharmaceuticals

Molecular biology based radiopharmaceuticals

Pharmacology and dosimetry of radiopharmaceuticals

Codes of GMP for radiopharmaceuticals

Centralized radiopharmacies

Regulatory aspects

Indigenous capacity building in radiopharmaceuticals

It is expected that the symposium will stimulate international exchange of information and ideas that will contribute to further enhancing the growth of developmental opportunities in nuclear medicine in general and in radiopharmaceutical chemistry in particular.