Phantom validation of coregistration of PET and CT for image-guided radiotherapy.

Radiotherapy treatment planning integrating positron emission tomography (PET) and computerized tomography (CT) is rapidly gaining acceptance in the clinical setting. Although hybrid systems are available, often the planning CT is acquired on a dedicated system separate from the PET scanner. A limiting factor to using PET data becomes the accuracy of the CT/PET registration. In this work, we use phantom and patient validation to demonstrate a general method for assessing the accuracy of CT/PET image registration and apply it to two multi-modality image registration programs. An IAEA (International Atomic Energy Association) brain phantom and an anthropomorphic head phantom were used. Internal volumes and externally mounted fiducial markers were filled with CT contrast and 18F-fluorodeoxyglucose (FDG). CT, PET emission, and PET transmission images were acquired and registered using two different image registration algorithms. CT/PET Fusion (GE Medical Systems, Milwaukee, WI) is commercially available and uses a semi-automated initial step followed by manual adjustment. Automatic Mutual Information-based Registration (AMIR), developed at our institution, is fully automated and exhibits no variation between repeated registrations. Registration was performed using distinct phantom structures; assessment of accuracy was determined from registration of the calculated centroids of a set of fiducial markers. By comparing structure-based registration with fiducial-based registration, target registration error (TRE) was computed at each point in a three-dimensional (3D) grid that spans the image volume. Identical methods were also applied to patient data to assess CT/PET registration accuracy. Accuracy was calculated as the mean with standard deviation of the TRE for every point in the 3D grid. Overall TRE values for the IAEA brain phantom are: CT/PET Fusion = 1.71 +/- 0.62 mm, AMIR = 1.13 +/- 0.53 mm; overall TRE values for the anthropomorphic head phantom are: CT/PET Fusion = 1.66 +/- 0.53 mm, AMIR = 1.15 +/- 0.48 mm. Precision (repeatability by a single user) measured for CT/PET Fusion: IAEA phantom = 1.59 +/- 0.67 mm and anthropomorphic head phantom = 1.63 +/- 0.52 mm. (AMIR has exact precision and so no measurements are necessary.) One sample patient demonstrated the following accuracy results: CT/PET Fusion = 3.89 +/- 1.61 mm, AMIR = 2.86 +/- 0.60 mm. Semi-automatic and automatic image registration methods may be used to facilitate incorporation of PET data into radiotherapy treatment planning in relatively rigid anatomic sites, such as head and neck. The overall accuracies in phantom and patient images are < 2 mm and < 4 mm, respectively, using either registration algorithm. Registration accuracy may decrease, however, as distance from the initial registration points (CT/PET fusion) or center of the image (AMIR) increases. Additional information provided by PET may improve dose coverage to active tumor subregions and hence tumor control. This study shows that the accuracy obtained by image registration with these two methods is well suited for image-guided radiotherapy.

Prospective feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET and CT imaging.

UNLABELLED: The aim of this investigation was to evaluate the influence and accuracy of (18)F-FDG PET in target volume definition as a complementary modality to CT for patients with head and neck cancer (HNC) using dedicated PET and CT scanners. METHODS: Six HNC patients were custom fitted with head and neck and upper body immobilization devices, and conventional radiotherapy CT simulation was performed together with (18)F-FDG PET imaging. Gross target volume (GTV) and pathologic nodal volumes were first defined in the conventional manner based on CT. A segmentation and surface-rendering registration technique was then used to coregister the (18)F-FDG PET and CT planning image datasets. (18)F-FDG PET GTVs were determined and displayed simultaneously with the CT contours. CT GTVs were then modified based on the PET data to form final PET/CT treatment volumes. Five-field intensity-modulated radiation therapy (IMRT) was then used to demonstrate dose targeting to the CT GTV or the PET/CT GTV. RESULTS: One patient was PET-negative after induction chemotherapy. The CT GTV was modified in all remaining patients based on (18)F-FDG PET data. The resulting PET/CT GTV was larger than the original CT volume by an average of 15%. In 5 cases, (18)F-FDG PET identified active lymph nodes that corresponded to lymph nodes contoured on CT. The pathologically enlarged CT lymph nodes were modified to create final lymph node volumes in 3 of 5 cases. In 1 of 6 patients, (18)F-FDG-avid lymph nodes were not identified as pathologic on CT. In 2 of 6 patients, registration of the independently acquired PET and CT data using segmentation and surface rendering resulted in a suboptimal alignment and, therefore, had to be repeated. Radiotherapy planning using IMRT demonstrated the capability of this technique to target anatomic or anatomic/physiologic target volumes. In this manner, metabolically active sites can be intensified to greater daily doses. CONCLUSION: Inclusion of (18)F-FDG PET data resulted in modified target volumes in radiotherapy planning for HNC. PET and CT data acquired on separate, dedicated scanners may be coregistered for therapy planning; however, dual-acquisition PET/CT systems may be considered to reduce the need for reregistrations. It is possible to use IMRT to target dose to metabolically active sites based on coregistered PET/CT data.

Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels.

The objective of this study was to target drug delivery to radiation-induced neoantigens, which include activated receptors within the tumor vasculature. These responses include posttranslational changes in pre-existing proteins, which can be discovered by phage-displayed peptide libraries administered to mice bearing irradiated tumors. Phage-displayed peptides recovered from irradiated tumors included the amino acid sequence RGDGSSV. This peptide binds to integrins within the tumor microvasculature. Immunohistochemical staining of irradiated tumors showed accumulation of fibrinogen receptor alpha(2b)beta(3) integrin. We studied tumor targeting efficiency of ligands to radiation-induced alpha(2b)beta(3). Radiopharmaceuticals were localized to irradiated tumors by use of alpha(2b)beta(3) ligands conjugated to nanoparticles and liposomes. Fibrinogen-conjugated nanoparticles bind to the radiation-activated receptor, obliterate tumor blood flow, and significantly increase regression and growth delay in irradiated tumors. Radiation-guided drug delivery to tumor blood vessels is a novel paradigm for targeted drug delivery.