Imaging delta- and mu-opioid receptors by PET in lung carcinoma patients

In the present study, we measured the kinetics and distribution in vivo of the selective delta-opioid antagonist 11C-methylnaltrindole (11C-MeNTI) and the mu-opioid agonist 11C-carfentanil (11C-CFN) in patients with lung carcinoma using PET.

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 - 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.

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 18F-FDG (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.

These data provide in vivo evidence for the presence of delta- and mu-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.