11C-choline prostate cancer imaging awaits next-generation technology

The fusion of 11C-choline PET data with high-resolution anatomic imaging (such as future hybrid PET/MRI systems) may offer the potential to guide targeted prostate biopsies and to noninvasively select high-risk prostate cancer patients for definitive treatments such as surgery or radiotherapy, according to research published in the October issue of the Journal of Nuclear Medicine.

“Hybrid PET/CT with 11C-choline has shown promise in the detection of primary prostate cancer associated with up-regulated choline kinase activity and increased choline retention,” wrote the authors of the study.

However, they noted that studies comparing 11C-choline imaging results with histology, whether from biopsies or prostatectomy specimens, suffer from considerable uncertainty about the true location of disease in relation to the imaging findings they are felt to represent.

The multi-disciplinary team from the University of Michigan in Ann Arbor assessed whether11C-choline PET/CT could identify high-risk primary adenocarcinoma of the prostate via the co-registration of anatomic, molecular and histological data.

They conducted 11C-choline PET/CT and trans-pelvic MRI on 14 men with untreated localized primary adenocarcinoma of the prostate, followed by radical prostatectomy as a form of primary monotherapy within 14 days of in vivo imaging.

All PET/CT exams were performed on either a Siemens Healthcare Biograph or Biograph TrueV HiRez system. The MRI exams were conducted with a 3-T MR Philips Healthcare Achieva system, using a transpelvic coil.

To minimize the disease location uncertainty that troubled other 11C-choline PET prostate cancer studies, the investigators obtained additional ex vivo MR images of the prostatectomy specimen to allow accurate co-registration of whole-mount histology with in vivo imaging.

“Nonlinear 3-dimensional image deformations were used for registrations of PET/CT, MRI, and histology,” the authors wrote. “Volumes of interest from tumor and benign tissue were defined on the basis of histology and were transferred into co-registered 11C-choline PET/CT volumes to calculate the mean and maximum ratio of tumor to benign prostate background.”

The results of the investigation indicate that increased 11C-choline uptake in primary prostate cancer is correlated with histologic surrogate markers of aggressiveness.

“On the basis of our data, the ratio between tumor and normal tissue is the key to identifying aggressive disease, whereas the absolute mean or maximum SUV [standardized uptake value] in a given lesion has less predictive value,” they wrote.

Although the early results on this small patient population appear promising, the research team noted that the difficulties in identifying benign prostatic tissues without sophisticated fusion techniques will limit their protocol’s potential for clinical applications. However, new technologies under development may hold the key to unlocking the potential of the 11C-choline biomarker for prostate cancer.

“As current state-of-the-art MRI of prostate cancer improves, future clinical hybrid PET/MRI will benefit lesion characterization by providing reliable anatomic image information, verifying (or disproving) the existence of a tumorous lesion at the site of focally increased 11C-choline uptake,” they observed. “If confirmed, such a lesion could—at the same time—be metabolically characterized by 11C-choline as being higher or lower risk. Hybrid PET/MRI may even include MRI spectroscopy, which recently has also shown promise in the identification of aggressive disease.”

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