NONSMALL CELL LUNG-CANCER FUNCTIONAL IMAGING - INCREASED HEXAKIS-2-METHOXY-ISOBUTYL-ISONITRILE TUMOR CLEARANCE CORRELATES WITH RESISTANCE TO CYTOTOXIC TREATMENT

Detection of P-glycoprotein and other multidrug resistance protein act ivity 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 a s a predictor for responses to chemotherapy but would also be of use i n testing the efficacy of multidrug resistance reversers in humans, Tc -99m radiolabeled hexakis-2-methoxyisobutyl-isonitrife (Tc-sestamibi) has been recently shown to be extruded from cells through P-glycoprote in activity, In the present study, we examined the uptake and extrusio n rate of the radiotracer in 25 patients with advanced nonsmall cell l ung cancer undergoing chest radiotherapy, using a novel scintigraphic technique based on simulation-guided pinhole imaging, Five-min tumor i mages were taken 10, 60, and 120 min postinjection of 20 mCi of Tc-ses tamibi, Six of 25 (24%) of tumors showed a 1.3-1.7 times higher extrus ion rate as compared to that of normal lung tissue, Increased tumor cl earance of Tc-sestamibi significantly correlated with resistance to ra diotherapy (P = 0.05) as well as the existence of distant metastasis ( P = 0.008), Patients with known resistance to chemotherapy had a highe r 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 imagi ng of lung cancer with Tc-sestamibi may have a role in predicting resp onses to cytotoxic treatment and in identifying tumors with aggressive behavior, Additional clinicopathological trials are required to inves tigate whether Tc-sestamibi kinetics correlates with P-glycoprotein ex pression, intratumoral angiogenesis, or other mechanisms.