Clinical production, stability studies and PET imaging with 16α- (¹⁸F) fluoroestradiol (16α-¹⁸F-FES): current status in India

Breast cancer remains the most common malignancy and a foremost cause of mortality in females worldwide. In India, breast cancer is now the most common cancer in most cities in India, and 2nd most common in the rural areas, one fourth (or even approaching one thirds) of all female cancer cases are breast cancers. The age shift (more young ladies affected),rising numbers of cases of breast cancer in India, late presentation (this directly decreases long term survival of the patients and lack of awareness and screening (screening is the single most important factor responsible for better survival of patients in the west) are some of areas which need urgent attention. In addition to early diagnosis, the understanding of oestrogen receptor (ER) levels in breast tumour is important for the prediction of disease prognosis and in deciding the appropriate treatment strategy. Oestrogens are the major role players in the initiation and progression of the breast cancer and approximately 75% of the tumours express the oestrogen receptor. Possibly for the first time in India, clinical production of ¹⁸F-FES has been carried out at Institute of Nuclear Medicine and Allied Sciences, Delhi. The synthesis of α-¹⁸Ffluoroestradiol was carried out using GE TRACERlab MX system with cyclic estradiol sulphate 3-O-methoxy –methyl-16b, 17b-epiestriol-Ocyclic sulfone (ABX) as precursor. Controlled synthesis of n.c.a. α-¹⁸F FES was carried out by nucleophilic substitution in 72 minutes. Cartridge method was used for the purification of the tracer. α-¹⁸F-FES was produced in 17-25% radiochemical yield (decay corrected). Chemical and radiochemical purity is >95% and >99% respectively. Results: Studies suggests α-¹⁸F-FES is an oestrogen receptor (ER)–specific PET tracer with various applications. α-¹⁸F-FES PET is being routinely utilized for assessing the expression of oestrogen receptors in cancer patients. More than 50 patients have benefitted from it and it has proved to a dependable tracer for the evaluation and management of breast cancer patients. Conclusions: With high incidences of ER (+) breast cancer cases, PET imaging with α-¹⁸F-FES has proved to a useful tool not only in the diagnosis of primary cancer but a vital tool for catering the patients with history of ER-positive breast cancer in whom a clinical dilemma remained despite complete standard work-up (e.g., when imaging procedures were inconclusive and performing a biopsy was not feasible). This knowledge is not only helping in the design of therapeutic trials to improve treatment outcomes, but also has the long term potential to help clinicians plan, target, and evaluate therapies. (author)