Multi-parametric PET/MRI With FDG and RGD for Enhanced Tumor Characterization of Patients With Cervical Cancer

Abstract Aim: The concept of personalized medicine has brought increased awareness to the importance of inter- and intra-tumor heterogeneity for cancer treatment. The aim of this study was to explore simultaneous multi-parametric PET/MRI prior to chemoradiotherapy for cervical cancer for characterization of tumors and tumor heterogeneity. Methods: Ten patients with histologically proven primary cervical cancer were examined with multi-parametric 68Ga-NODAGA-E[c(RGDyK)]2-PET/MRI for radiation treatment planning after diagnostic 18F-FDG-PET/CT. Standardized uptake values (SUV) of RGD and FDG, diffusion weighted MRI and the derived apparent diffusion coefficient (ADC), and pharmacokinetic maps obtained from dynamic contrast-enhanced MRI with the Tofts model (iAUC60, Ktrans, ve, and kep) were included in the analysis. The spatial relation between functional imaging parameters in tumors was examined by a correlation analysis and joint histograms at the voxel level. The ability of multi-parametric imaging to identify tumor tissue classes was explored using an unsupervised 3D Gaussian mixture model-based cluster analysis.Results: Functional MRI and PET of cervical cancers appeared heterogeneous both between patients and spatially within the tumors, and the relations between parameters varied strongly within the patient cohort. The strongest spatial correlation was observed between FDG uptake and ADC (median r=-0.7). There was moderate voxel-wise correlation between RGD and FDG uptake, and weak correlations between all other modalities. Distinct relations between the ADC and RGD uptake as well as the ADC and FDG uptake were apparent in joint histograms. A cluster analysis using the combination of ADC, FDG and RGD uptake suggested tissue classes which could potentially relate to tumor sub-volumes. Conclusion: A multi-parametric PET/MRI examination of patients with cervical cancer integrated with treatment planning and including estimation of angiogenesis and glucose metabolism as well as MRI diffusion and perfusion parameters is feasible. A combined analysis of functional imaging parameters indicates a potential of multi-parametric PET/MRI to contribute to a better characterization of tumor heterogeneity than the modalities alone. However, the study is based on small patient numbers and further studies are needed prior to the future design of individually adapted treatment approaches based on multi-parametric functional imaging.

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Clinical characterization of hypoxia in pancreatic ductal adenocarcinoma (PDAC) by 18F-FAZA PET and pimonidazole.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4049 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4049-4049

Author(s):

Cristiane Metran Nascente ◽

Neesha C. Dhani ◽

Douglass Vines ◽

Ivan Yeung ◽

Ur Metser ◽

...

Keyword(s):

Functional Imaging ◽

Tumor Biology ◽

Automated Image Analysis ◽

Ductal Adenocarcinoma ◽

Significant Heterogeneity ◽

Reference Tissue ◽

Pet Tracer ◽

Standardized Uptake Values ◽

Positron Emission

4049 Background: We previously demonstrated correlation between hypoxia and aggressive tumor biology in orthotopic, patient-derived pancreatic xenografts (Chang et al. Cancer Res 2011). With the development of hypoxia-directed therapies, there is a need to understand the range and relevance of hypoxia in PDAC patients. We therefore launched two complementary clinical trials using 2-nitroimidazole-based hypoxia probes. Methods: PIMO-PANC involves pre-operative administration of pimonidazole to patients (pts) undergoing PDAC resection. Hypoxic percent (HP) of tumors is determined by semi-automated image analysis (on Aperio’s Genie) of multiple histological sections stained for pimonidazole by immunohistochemistry (IHC). FAZA-PANC uses the positron emission tomography (PET) tracer fluoroazomycin arabinoside (18F-FAZA) to evaluate hypoxia by functional imaging. 2 hours post-injection of (5.2 MBq/kg) 18F-FAZA, static scans are acquired followed by computed tomography for anatomic registration. Skeletal muscle is a non-hypoxic reference tissue to define standardized uptake values (SUV), tumor to muscle uptake ratios (T/M’s) and a threshold for hypoxia. Results: PIMO-PANC has enrolled 29 pts and FAZA-PANC 16. IHC analysis of the first 10 pt tumors demonstrates considerable intra- and inter-tumoral heterogeneity of hypoxia (HP: 1 to 26% across pt tumors); minimal hypoxia (< 5%) was observed in 3 pts. 18F-FAZA-PET in the first 11 pts demonstrates SUVmax from 1.02 to 1.83, median T/M's from 0.84 to 1.31. A threshold of 1.27 SUVmax defines HP of 0 to 60% with minimal hypoxia (<10%) in 5 pts. Conclusions: There is significant heterogeneity of hypoxia across the spectrum of clinical PDAC (local to metastatic disease) using the 2-nitroimidazole hypoxia probes pimonidazole and 18F-FAZA. Given the intra-tumoral heterogeneity of hypoxia by histopathology, functional imaging is the preferred method to assess hypoxia in PDAC patients. Importantly, both methods identified a group of PDAC tumors with low levels of hypoxia. This is relevant to the on-going development of hypoxia-targeting strategies. Accrual to PIMO-PANC is on-going and will address the prognostic relevance of hypoxia in PDAC. Clinical trial information: NCT01542177 and NCT01248637.

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