Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are tumor markers of small cell lung cancer (SCLC) which were reported to predict outcome of patients with SCLC. We previously reported that dipyridamole-modulated Tc-99m sestamibi (dipyridamole-MIBI) single photon emission computed tomography (SPECT) could predict the response to chemotherapy in SCLC patients. The purpose of this study was to compare dipyridamole-MIBI and pretreatment serum levels of NSE and LDH for the prediction of response to chemotherapy in SCLC. Twenty-eight SCLC patients underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at lease two cycles). Serum levels of NSE and LDH were also measured at the same day of the imaging. Tomographic images before and after 0.84 mg/kg dipyridamole infusion were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete (CR), partial response (PR), no change (NC), and progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. Among the 28 patients, 15 were responders (2 CR, 13 PR) and 13 were nonresponders (11 NC, 2 PD). The change of tumor-to-normal lung ratio (T:NL) after infusion of dipyridamole was significantly higher in responders as compared with nonresponders (0.38 +/- 0.64 vs. -0.38 +/- 0.50, respectively, p = 0.002). However, pretreatment serum NSE and LDH levels did not correlate with the response to chemotherapy. Increase of T:NL after dipyridamole infusion was a strong negative predictor of chemotherapeutic response in SCLC patients, while NSE and LDH could not predict it.