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Imaging - and µ-Opioid Receptors by PET in Lung Carcinoma Patients

¹ Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; ² Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland; and ³ Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Correspondence: For correspondence or reprints contact: Igal Madar, PhD, JHOC 4230, 601 N. Caroline St., Baltimore, MD 21287. E-mail: imadar{at}jhmi.edu

In the present study, we measured the kinetics and distribution in vivo of the selective -opioid antagonist ¹¹C-methylnaltrindole (¹¹C-MeNTI) and the µ-opioid agonist ¹¹C-carfentanil (¹¹C-CFN) 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 – 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 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. Conclusion: These data provide in vivo evidence for the presence of - 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.

Key Words: PET • lung carcinoma • opioid receptor

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