Application of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET imaging to predict highly malignant tumor grades and hypoxia-inducible factor-1α expression in patients with glioma.
OBJECTIVE
Hypoxic tissue evaluation in glioma is important for predicting treatment response and establishing antihypoxia therapy. In this preliminary study, (62)Cu-ATSM PET was used to determine its validity as a biomarker for distinguishing tumor grade and tissue hypoxia.


METHODS
(62)Cu-ATSM PET was performed in 22 patients with glioma, and the (62)Cu-ATSM SUV(max) and T/B ratio were semiquantitatively evaluated. (62)Cu-ATSM uptake distribution was qualitatively evaluated and compared with MR imaging findings. HIF-1α expression, a hypoxia marker, was compared with (62)Cu-ATSM uptake values.


RESULTS
The (62)Cu-ATSM SUV(max) and T/B ratio were significantly higher in grade IV than in grade III gliomas (P = .014 and .018, respectively), whereas no significant differences were found between grade III and grade II gliomas. At a T/B ratio cutoff threshold of 1.8, (62)Cu-ATSM uptake was predictive of HIF-1α expression, with 92.3% sensitivity and 88.9% specificity. The mean T/B ratio was also significantly higher in HIF-1α-positive glioma tissue than in HIF-1α-negative tissue (P = .001). Using this optimal threshold of T/B ratio, (62)Cu-ATSM PET showed regional uptake in 61.9% (13/21) of tumors within the contrast-enhanced region on MR imaging, which was significantly correlated with presence of a necrotic component (P = .002).


CONCLUSIONS
Our results demonstrated that (62)Cu-ATSM uptake is relatively high in grade IV gliomas and correlates with the MR imaging findings of necrosis. Moreover, the (62)Cu-ATSM T/B ratio showed significant correlation with HIF-1α expression. Thus, (62)Cu-ATSM appears to be a suitable biomarker for predicting highly malignant grades and tissue hypoxia in patients with glioma.
Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
K
K
Tateishi
U
U
Tateishi
M
M
Sato
S
S
Yamanaka
H
H
Kanno
H
H
Murata
T
T
Inoue
N
N
Kawahara
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D056831:Coordination Complexes; D003301:Copper Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013882:Thiosemicarbazones / Q000493:pharmacokinetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; D056831:Coordination Complexes; D003301:Copper Radioisotopes; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)