Objective: Tumor hypoxia can influence response to radiotherapy and other treatment modalities. Oxygenation status is proved to be an independent prognostic factor. 99mTc-HL91 (99mTc labeled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime) is a potential noninvasive marker of tumor hypoxia. It has been reported that 99mTc-HL91 has certain validity for hypoxia imaging. But its clinical study had not been reported widely. This study was carried out to evaluate the relationship between the T/N ratio of HL91 SPECT hypoxia imaging and the radiotherapeutic outcome.

Methods: 32 patients with pathologically proven non-small cell lung cancer received three-dimensional conformal radiotherapy were enrolled into the study. 99mTc-HL91 SPECT scanning was performed in all patients at one or two days before radiotherapy. It was also performed in 18 patients at one or two days after the onset of radiotherapy, when they received a dose of 30 - 40 Gy already. Anterior, posterior and lateral planar images were collected at 2, 4 and 6 hours, respectively, after intravenous injection of approximately 740 MBq 99mTc-HL91. Regions of interest (ROIs) were drawn in the tumor and the contralateral normal lung tissue, and the radioactivity ratio of tumor to normal tissue (T/N) was calculated. To assess whether the tumor uptake of 99mTc-HL91 is predictive of treatment response, the SPECT results were correlated with the results of clinical follow-up.

Results: The relationship between T/N ratios at 4 h images after injection was shown to be the best of three acquired images before radiotherapy. The response and overall survival to radiotherapy were analyzed for all 32 patients. The results of 9mTc-HL91 correlated well with radiotherapy response (P = 0. 002) and also patients' survival (P = 0.043). The average T/N values of 18 patients who received serial scanning were 1.57 +/- 0.18, 1.44 +/- 0.19 and 1.30 +/- 0.14, respectively. There was a significant difference between those three groups (P = 0. 000). The T/N changes during radiotherapy were not associated with the treatment outcome.

Conclusion: HL91 SPECT imaging can identify the hypoxia status and changes during radiotherapy in lung cancer. Hypoxia SPECT imaging with HL91 before treatment may predict radiotherapy response and patients' survival. Longer follow up in more patients is planned to confirm this result.

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