Technetium-99m tetrofosmin (TF) is a myocardial perfusion agent that has recently proved useful also as tumor-seeking tracer. The aim of this study was to make a preliminary assessment of TF scintigraphy in osteosarcoma, with regard to tumor detection and monitoring of response to preoperative chemotherapy (PC). Current clinical investigations have demonstrated that the curability of osteogenic sarcoma mainly depends on the response to PC, and the percentage of tumor necrosis is the most powerful prognostic factor. However, this is difficult to assess radiologically, and it can only been obtained by histologic examination after surgery. Fourteen patients (7 males, age range: 1-17 years) with recently discovered osteosarcoma of the extremities or the pelvis were injected with TF ( approximately 7.4 MBq/kg i.v., never in the affected limb): a dynamic acquisition (20 min) was performed immediately post-injection, followed by static planar views of the involved area. Six patients were studied twice: before and after PC. Images were evaluated visually and quantitatively using regions of interest over lesion (L) and controlateral normal tissue (N). All initial TF scans demonstrated very rapid tumoral uptake (1-2 min post-injection); the mean L/N ratio at 20 min was 2.76+/-1.05. The post-PC scans showed reduced uptake in 4 patients, unchanged in one and increased accumulation in one case, with a strong correlation between the percentage change in L/N and the percentage of tumor necrosis. Our preliminary data indicate that TF is able to detect osteosarcoma; further studies including larger population is need to confirm its usefulness in non-invasively predicting response to PC.