REDIFFERENTIATION THERAPY-INDUCED RADIOIODINE UPTAKE IN THYROID-CANCER

Due to a dedifferentiation of tumor cells, some thyroid carcinomas los e their capability for radioiodine (RI) concentration. This phenomenon is associated with a worse prognosis and prevents effective treatment . Retinoic acid (RA) is known to induce redifferentiation in various k inds of tumors and has been used recently in thyroid cancer. Methods: Twelve patients (9 women, 3 men) with 6 papillary, 4 follicular and 2 mixed-cell type tumors (including 4 Hurthle cell carcinomas) were trea ted orally with RA (dose: 1.18 +/- 0.37 mg/kg body weight) for at leas t 2 mo before RI therapy. None of the patients could be treated with a ny other modality (RI, surgery, external radiation) when RA administra tion was started. Initially, clinically important tumor sites did not take up significant amounts of RI, Changes of RI uptake and thyroglobu lin (Tg) serum values were determined. Glucose metabolism was followed with fluorodeoxyglucose (FDG) PET imaging in 10 patients before and i n 5 patients after RA treatment. Results: In 2 patients, a significant RI uptake was induced by RA, and in another 3 patients a faint RI upt ake was achieved (responder group). In 7 patients, no change of RI upt ake was observed (nonresponder group). Median Tg was increased from 10 5-840 mu g/liter during RA therapy in the responder group, which was s ignificantly higher than the nonresponder group (173-134 mu g/liter). FDG PET was positive in all 10 patients before RA therapy. PET showed variable patterns of changes (increase/decrease/disappearance) in gluc ose consumption related to RA response. Conclusion: RA can induce RI u ptake in some patients with RI negative thyroid carcinoma tumor sites. Response to RA is associated with a significantly higher increase of Tg, suggesting that a restoration of Tg synthesis can be addressed as a redifferentiation parameter in these patients.