The potential of PET: a closer look

The last decade has seen numerous publications demonstrating the advantages of combining morphological and functional imaging, and with commercial PET/CT scanners emerging in the same time frame, PET/CT has already had a significant impact on patient management. Ultimately, molecular-imaging-guided radiotherapy holds the promise of improved definition of tumour target volumes. Yet, despite considerable progress to date, challenges remain if we are to fully exploit the potential of PET/CT-guided radiotherapy treatment planning.

With this in mind, Habib Zaidi, head of the PET Instrumentation & Neuroimaging Laboratory at Geneva University Hospital in Switzerland and associate professor at the University Medical Center Groningen in the Netherlands, has conducted a detailed review of recent progress in PET/CT technology. In particular, Zaidi and co-authors examined the potential of using PET/CT imaging for radiotherapy treatment planning (Acad. Radiol. doi: 10.1016/j.acra.2009.02.014).

Parallel progress
Zaidi explains that the growing prevalence of PET/CT was stimulated both by advances in dual-modality imaging technologies and progress in radiation delivery techniques. The emergence of commercial dual-modality systems, for example, brought considerable advantages: PET/CT can produce anatomical and functional images during a single procedure and with the patient in the same position, greatly simplifying the image registration and fusion processes.

The resulting images are complementary: PET can identify areas of disease not seen via CT, while the CT study provides an anatomical context. CT also provides a patient-specific map of attenuation coefficients with which to correct the PET emission data, thus improving the quantitative accuracy of the correlated PET data as well as the image quality.

There's also been renewed interest in areas such as time-of-flight PET, due to faster scintillation crystals and electronics making this approach commercially feasible. Meanwhile, progress in CT technology has led to the introduction of 256- and 320-slice CT scanners. Zaidi highlights one particular development - the recent introduction of hybrid PET/MRI technology - as a major breakthrough in the field and an area that's now under investigation by several research groups. He notes that a prototype for simultaneous PET/MRI brain imaging (BrainPET) is already being assessed in a clinical setting.

The power of PET lies in the radiotracer, with ¹⁸F-fluorodeoxyglucose (FDG) - used to image tumour metabolism - currently the most prevalent PET probe. In fact, the authors argue that FDG-PET has made an everlasting impact on the specialty of nuclear medicine. "It is not an exaggeration to speculate that in the coming years, the number of FDG-PET images performed in most facilities will exceed that of all other procedures performed with radiolabelled compounds," they write.

Asides FDG, other PET tracers have emerged over the last few years. The most significant include markers of tumour proliferation, amino acid metabolism and hypoxia, which have already shown their importance in radiotherapy target volume delineation or patient management. Zaidi expects that several new tracers will be approved and enter routine clinical use in the coming years.

As for the advances in radiotherapy - Zaidi cites developments including stereotactic radiosurgery and radiotherapy, particle therapies, tumour-motion compensation schemes and image-guided radiation therapy as key, and in particular, intensity-modulated radiation therapy (IMRT). IMRT's ability to deliver highly conformal radiation dose distributions results in a need for more accurately target definition. It's been suggested that molecular imaging using PET/CT may be of particular value here, enabling a more correct delineation of gross tumour volume and planning target volume. Zaidi emphasizes that much scientific research and clinical studies are needed before this potential can be fully realized.

Planning potential
The availability of multislice hybrid PET/CT scanners has enabled diagnostic PET/CT and radiotherapy planning CT to be performed in a single session. This scheme is being routinely used in many institutions and is the subject of an increasing number of research studies. The ability to image tumour metabolism further prompted the idea of defining a "biologic" target volume that incorporates tumour biology into the treatment planning, with FDG-PET/CT-based target volume delineation studied by various research groups for a range of malignancies.

In head-and-neck cancers, for example, it has been reported that using pre-treatment FDG-PET and pre-treatment CT or MRI significantly impacts the delineation of target volumes in pharyngo-laryngeal squamous-cell carcinoma, resulting in more normal tissue sparing after conformal RT planning. Comparisons of standard imaging techniques and PET findings showed that target volumes based on FDG-PET were significantly smaller and correlated better with pathologic findings than CT.

Other indications that may well benefit from FDG-PET target-volume delineation include non-small-cell lung cancer (in which FDG-PET is well established for staging and has made a documented impact on clinical decision making), as well as oesophageal cancer, colorectal cancer, cervical cancer, lymphoma and breast cancer. For the latter, Zaidi highlights the emergence of dedicated breast PET scanners that achieve higher spatial resolution and improved sensitivity.

The authors note that while initial findings are encouraging, they need to be confirmed by prospective studies before PET/CT-guided radiotherapy can be used clinically with confidence. They point out that one of the main difficulties of PET-based treatment planning is the accurate delineation of target volume from noisy PET data. Several PET segmentation algorithms have been developed so far with limited success.

Zaidi's research group recently developed two novel automated techniques that allow unsupervised quantification of tumour volumes. The first one was published in 2007 (Med. Phys. 34 722) while the second will be presented later this month at the Society of Nuclear Medicine's annual meeting in Toronto, Canada. The team has also assessed the potential of various strategies for gross tumour volume delineation of brain tumour using ¹⁸F-fluoro-ethyl-typosine as a probe (Eur. J. Nucl. Med. Mol. Imaging 36 182).

Another challenge for the industry is to provide a vendor-independent platform that can incorporate PET/CT data, in a DICOM-compatible format, into treatment-planning software.

Zaidi says that one particular concern is the limited exposure that many radiation oncologists have had to hybrid technologies. "A joint effort between experienced nuclear medicine physicians and radiation oncologists is therefore a prerequisite to fully exploit the potential of PET/CT-guided radiotherapy," the authors write, suggesting that discussions should take place between nuclear-medicine and radiation-oncology professional societies to help define training requirements and guidelines.

The authors conclude that, despite the remarkable progress achieved in molecular-imaging-guided radiotherapy planning, as witnessed by an enormous number of publications in the field, many challenging issues still remain to be solved.