title: In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM.
abstract: Tumor hypoxia is recognized as an important determinant of response to therapy. In this study we investigated the feasibility of clinical imaging with copper-60 diacetyl-bis( N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of (60)Cu-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with (60)Cu-ATSM before initiation of therapy. (60)Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M). All patients also underwent PET with fluorine-18 fluorodeoxyglucose (FDG) prior to institution of therapy. The PET results were correlated with follow-up evaluation (2-46 months). It was demonstrated that PET imaging with (60)Cu-ATSM in patients with NCSLC is feasible. The tumor of one patient had no discernible (60)Cu-ATSM uptake, whereas the tumor uptake in the remaining patients was variable, as expected. Response was evaluated in 14 patients; the mean T/M for (60)Cu-ATSM was significantly lower in responders (1.5+/-0.4) than in nonresponders (3.4+/-0.8) (P=0.002). However, the mean SUV for (60)Cu-ATSM was not significantly different in responders (2.8+/-1.1) and nonresponders (3.5+/-1.0) ( P=0.2). An arbitrarily selected T/M threshold of 3.0 discriminated those likely to respond to therapy: all eight responders had a T/M <3.0 and all six nonresponders had a T/M > or =3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P=0.7) and did not correlate with (60)Cu-ATSM uptake (r=0.04; P=0.9). (60)Cu-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of (60)Cu-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.
authors.affiliation: Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, St. Louis, MO 63110, USA. dehdashtif@mir.wustl.edu
authors.forename: Farrokh
authors.initials: F
authors.lastname: Dehdashti
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bradley
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.forename: Richard
authors.initials: R
authors.lastname: Laforest
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Barry A
authors.initials: BA
authors.lastname: Siegel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D015687:Cell Hypoxia / Q000502:physiology*; D056831:Coordination Complexes; D003301:Copper Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019047:Phantoms, Imaging; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013882:Thiosemicarbazones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014055:Tomography, Emission-Computed; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)