P280, a synthetic peptide composed of 26 aminoacids, has high affinity (Kd = 100 nM) and specificity for the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor expressed on activated platelets. In this study we investigated the potential usefulness of imaging deep vein thrombosis (DVT) and pulmonary embolism (PE) in humans with 99mTc-P280. In 15 patients (9 men and 6 women; mean age +/- s.d.: 49.2 +/- 14.1) with known DVT and/or PE, serial images were acquired within 24 hours of the injection of approximately 200 micrograms of P280 radiolabelled with 10-23 mCi of 99mTc. P280 was labelled with the ligand exchange method using 99mTc-glucoheptonate. Rapid blood clearance (< or = 5% ID was still circulating in 1 hour) enabled identification of thrombi as early as 60 minutes after the injection, with significant thrombi-to-background ratios (range: 2-4) in 11/15 patients (73%), in 7/9 with DVT, in 2/3 with PE and in 2/3 patients with both DVT and PE. Radiotracer uptake was clearly detectable also in late scans, which confirms that 99mTc-P280 specifically binds to the thrombi through a receptor-mediated mechanism. PE localizations were detectable 3-4 hours after peptide injection, and in 2 cases SPECT enabled the detection of thrombi missed on planar views. Conversely, the test was negative in 4 patients who had the onset of clinical symptoms and the diagnosis of DVT and/or PE more than 40 days before scintigraphy. The lack of 99mTc-P280 uptake in the latter patients suggested that the peptide does not bind to thrombi when thrombogenesis is not active. These preliminary results clearly indicate scintigraphy with 99mTc-P280 to be a suitable, noninvasive and highly specific tool to image fresh clots causing DVT and/or PE. Thus, this technique might overcome the limitations of the imaging procedures currently in use.