Imaging δ- and μ-opioid receptors by PET in lung carcinoma patients

In the present study, we measured the kinetics and distribution in vivo of the selective δ-opioid antagonist ¹¹C-methylnaltrindole ( ¹¹C-MeNTI) and the μ-opioid agonist ¹¹C-carfentanil (¹¹CCFN) in patients with lung carcinoma using PET. Methods: Paired measurements of ¹¹C-MeNTI and ¹¹C-CFN binding were performed in biopsy-proven small-cell (n = 2), squamous (n = 2), and adenocarcinoma (n = 3) lung cancer patients. Dynamic PET scans of increasing duration (0.5-8 min) were acquired over 90 min after an intravenous bolus injection of 370 MBq of tracer. Time-activity curves for tumor and normal lung parenchyma binding were generated using the region-of-interest (ROI) method. The mean activity at equilibrium was measured, and the specific-to-nonspecific binding ratio (tumor 2 lung)/lung was calculated. Four of 7 patients underwent an additional static ¹⁸F-FDG PET scan for clinical indications. Three of 7 patients underwent surgery, and stained sections of tumor were inspected for inflammation, necrosis, and scar tissue. Results: Increased binding of ¹¹C-MeNTI and ¹¹C-CFN was detected in all tumor types studied. ¹¹C-MeNTI binding in tumor and healthy lung tissue was significantly more intense than that of ¹¹C-CFN. The average specific-to-nonspecific binding ratio across cell types for ¹¹C-MeNTI (4.32 ± 1.31; mean ± SEM) was greater than that of ¹¹C-CFN (2.42 ± 1.17) but lower than that of ¹⁸FFDG (7.74 = 0.53). Intravenous naloxone produced 50% and 44% decreases in the specific-to-nonspecific binding ratios of ¹¹C-MeNTI and ¹¹C-CFN, respectively. Conclusion: These data provide in vivo evidence for the presence of δ- and μ-opioid receptor types in the 3 major human lung carcinomas and suggest the suitability of ¹¹C-MeNTI and ¹¹C-CFN as investigational probes of lung carcinoma biology.