title: Non-small cell lung cancer functional imaging: increased hexakis-2-methoxy-isobutyl-isonitrile tumor clearance correlates with resistance to cytotoxic treatment.
abstract: Detection of P-glycoprotein and other multidrug resistance protein activity is currently under investigation to identify subgroups of cancer patients with tumors resistant to chemotherapy. Application of a test that reliably evaluates the phenomenon in vivo would not only serve as a predictor for responses to chemotherapy but would also be of use in testing the efficacy of multidrug resistance reversers in humans. Tc-99m radiolabeled hexakis-2-methoxy-isobutyl-isonitrile (Tc-sestamibi) has been recently shown to be extruded from cells through P-glycoprotein activity. In the present study, we examined the uptake and extrusion rate of the radiotracer in 25 patients with advanced non-small cell lung cancer undergoing chest radiotherapy, using a novel scintigraphic technique based on simulation-guided pinhole imaging. Five-min tumor images were taken 10, 60, and 120 min postinjection of 20 mCi of Tc-sestamibi. Six of 25 (24%) of tumors showed a 1.3-1.7 times higher extrusion rate as compared to that of normal lung tissue. Increased tumor clearance of Tc-sestamibi significantly correlated with resistance to radiotherapy (P = 0.05) as well as the existence of distant metastasis (P = 0.008). Patients with known resistance to chemotherapy had a higher extrusion rate as compared to chemotherapy-naive patients (P = 0.01). Moreover, increased Tc-sestamibi tumor capture was seen in patients with distant metastasis (P = 0.09). We concluded that functional imaging of lung cancer with Tc-sestamibi may have a role in predicting responses to cytotoxic treatment and in identifying tumors with aggressive behavior. Additional clinicopathological trials are required to investigate whether Tc-sestamibi kinetics correlates with P-glycoprotein expression, intratumoral angiogenesis, or other mechanisms.
authors.affiliation: Departments of Radiation & Medical Oncology and Nuclear Medicine, University Hospital of Iraklion, Iraklion 71110, Crete, Greece.
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: S
authors.initials: S
authors.lastname: Koukouraki
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: J
authors.initials: J
authors.lastname: Skarlatos
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: N
authors.initials: N
authors.lastname: Karkavitsas
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics; D014018:Tissue Distribution; D017211:Treatment Failure
chemical_list: D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi