Article

Assessing tumor hypoxia in cervical cancer by PET with Cu-60-labeled diacetyl-bis(N-4-methylthiosemicarbazone)

Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110, USA.
Journal of Nuclear Medicine (Impact Factor: 5.56). 02/2008; 49(2):201-5. DOI: 10.2967/jnumed.107.048520
Source: PubMed

ABSTRACT Tumor hypoxia indicates a poor prognosis. This study was undertaken to confirm our prior pilot results showing that pretreatment tumor hypoxia demonstrated by PET with (60)Cu-labeled diacetyl-bis(N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) is a biomarker of poor prognosis in patients with cervical cancer. Thirty-eight women with biopsy-proved cervical cancer underwent (60)Cu-ATSM PET before the initiation of radiotherapy and chemotherapy. (60)Cu-ATSM uptake was evaluated semiquantitatively as the tumor-to-muscle activity ratio (T/M). A log-rank test was used to determine the cutoff uptake value that was strongly predictive of prognosis. All patients also underwent clinical PET with (18)F-FDG before the institution of therapy. The PET results were correlated with clinical follow-up. Tumor (60)Cu-ATSM uptake was inversely related to progression-free survival and cause-specific survival (P = 0.006 and P = 0.04, respectively, as determined by the log-rank test). We found that a T/M threshold of 3.5 best discriminated patients likely to develop a recurrence from those unlikely to develop a recurrence; the 3-y progression-free survival of patients with normoxic tumors (as defined by T/M of < or = 3.5) was 71%, and that of patients with hypoxic tumors (T/M of > 3.5) was 28% (P = 0.01). Tumor (18)F-FDG uptake did not correlate with (60)Cu-ATSM uptake, and there was no significant difference in tumor (18)F-FDG uptake between patients with hypoxic tumors and those with normoxic tumors (P = 0.9). Pretherapy (60)Cu-ATSM PET provides clinically relevant information about tumor oxygenation that is predictive of outcome in patients with cervical cancer.

1 Follower
 · 
87 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[18¿F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N4)-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models.Methods Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients.ResultsComparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions.Conclusion Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting strategy in radiotherapy treatment planning.
    Radiation Oncology 10/2014; 9(1):228. DOI:10.1186/s13014-014-0228-0 · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: FDG-PET/CT has been evaluated in a variety of gynecologic malignancies in a variety of settings and is approved by the Centers for Medicare & Medicaid Services for the initial and subsequent treatment strategies of these malignancies. Cervical cancer is typically very FDG avid, and FDG-PET/CT appears to be most valuable for initial staging, radiation therapy planning, and detection of recurrent disease. For ovarian cancer, the most value of FDG-PET/CT appears to be for detecting recurrent disease in the setting of rising CA-125 level and negative or equivocal anatomical imaging studies. Initial studies evaluating response to therapy are promising and further work in this area is needed. FDG uptake in both nonmalignant and physiological processes in the pelvis can make interpretation of FDG-PET/CT in this region challenging and knowledge of these entities and patterns can avoid misinterpretation. Some of the most common findings relate to the cyclic changes that occur as part of the menstrual cycle in premenopausal women. Mucinous tumors and low-volume or peritoneal carcinomatosis are causes of false-negative results on FDG-PET/CT studies. As new tracers are developed, comparisons with patient outcomes and standards of care (eg, FDG-PET/CT) will be needed.
    Seminars in Nuclear Medicine 11/2014; 44(6):461-478. DOI:10.1053/j.semnuclmed.2014.06.005 · 3.13 Impact Factor

Preview

Download
0 Downloads
Available from