(PET in Radiotherapy Planning)
Imaging modality plays a great role in treatment planning.
Positron emission tomography PET has been used in treatment planning in the delineation of Gross target volume GTV which is considered as the most important component in treatment planning. Also, PET Accuracy in the delineation of GTV impact on dose delivery to tumor tissue while delivering a low dose rate to healthy tissue or critical structure surrounding the tumor. PET has great sensitivity and specificity in the delineation of Gross target volume more than other imaging modality that has been used in treatment planning. because PET uses FDG and these an advantage that reduces the uncertainty in defining tumor margin in radiotherapy treatment planning. [1]
Recently PET imaging or molecular imaging has been used in treatment planning for cancer patients. By using PET radiotracer 18F-FDG which allow viewing the molecular pathways for the target (tumor), metabolism, proliferation, oxygen delivery, and consumption many receptors or gene expression.
Using PET images in treatment planning can give us information about tumor response to radiotherapy, can localize the reoccurring tumors in an early stage. The most important function of PET imaging in treatment planning Delineation of tumor or target and organ at risk OAR. [9] Positron emission tomography PET, has an advantage in cancer patient management by using 18F-FDG as a tracer helps in the delineation of the target volume in non-small cell lung cancer NSCLC patients, head and neck squamous cell carcinoma HNSCC, and rectal carcinomas.[9] There is another PET radiotracers differ in their sensitivity and specificity which impact the image and the treatment planning.
FDG it has non- specific uptake in tumor and high uptake in other areas such as infection or inflammation sites.[9][10] hypoxia imaging with PET a useful tool to know tumor response during radiotherapy treatment or identify the resistant tumor cells, and to deliver the higher radiation dose to the parts that radio-resistant which have a higher chance of tumor reoccurrence. [4] the best PET tracer should have these properties high uptake values in the tumor, high sensitivity and specificity in tumor site, low production cost, and availability.[5]
The first use of PET-FDG was with non-small cancer lung cells NSCLC by accurate delineation for nodal and distant metastases. FDG-PET has been used with CT images due to the poor spatial resolution of FDG-PET.[9] FDG-PET more accurate than CT in localizing mediastinal nodal in SCLC, also FDG-PET helps to reduce the isolated nodal failures outside the clinical target volume CTV.[9] The resolution limits for PET 5-7mm, any object lower than this limit will have a weak signal which affects the resulting image.[9] Due to this limitation, there is the uncertainty of estimating the real tumor size. PET images may contain a signal noise. [12] FDG used as a guide through the segmentation process, then these segments combined to form the large target region. The main objective of segmentation to determine which part of the target will receive the primary dose and which one will have the higher dose GTV.[10] PET-avid delivery of a nonhomogeneous dose of FDG-PET to the target region, by concerted the higher dose to the avid region and lower dose to the OAR or keep the dose below the threshold of deterministic effects.[10] the disadvantage of FDG is non-specific uptakes values for tumor due to the high activity of glucose. [5]
Using FDG-PET with CT handle the limitation of low spatial resolution of PET. [9] Fusing PET images with CT images improve the accuracy of delineation, and high sensitivity, and specificity (96.6%) of tumor detection and contributed in treatment decision based on the changing of GTV. [11] since CT provides electron density data that improve the dose calculation in treatment planning. [12] Using two imaging modalities enhance the detection of reoccurrence tumors especially colorectal cancers.[11] Fusing techniques: (1) Hybrid PET/CT fusing the images in the system by RTP and (2) Fusing PET and CT images separately and two registration methods: (1) rigid and (2) deformable. In PET/CT it is important that immobilization device fits with PET/CT, immobilization device such as masks and shoulder in head and neck cancer easily fits with PET/CT. PET/CT has been used in gate acquisition of lung and thoracic and excellent bowel preparation of abdominopelvic malignancies. Both PET and CT have artifacts due to patient motion especially respiratory motion which lead to the wrong estimation of SUV and tumor size. Inaccurate SUV due to a mismatch between PET and CT because of the difference in time acquisition. PET has superior sensitivity and specificity over CT in lung cancer helps to improve the therapeutic ratio by increasing the dose in the target site and minimize the dose in OAR and normal tissue. There is two correction techniques of respiratory motion 4D PET/CT, DIBH PET/CT. [12]
18F-fluorothymidine FLT it is cellular proliferation, phosphorylated by thymidine kinase in active cells and trapped in the cell but does not marker DNA.[9][10] FLT is excellent images for tumor volume changes due to radiotherapy. [13] FLT can give information about the tumor response during the treatment course. After 15 to 18 fractioned doses (4thweek) chances in GTV is detectable. The uptake values of FLT decrease due to the reduction of tumor cell density during the treatment and this is impacting on the FLT signal.[14]
[9][10]
The sensitivity of 11C-methionine PET in brain tumor is higher than FDG-PET due to the high activity of glucose in normal brain tissue. This is making 11C-methionine the best PET tracer for brain tumor delineation. [5] 11C-methionine provides biological information about the tumor and the response to treatment. 11C-methionine helps in diagnosis identify the tumor activity with primary and recurrent gliomas patients.[15] tumor grading may be estimated incorrectly in brain tumor especially gliomas kind because it is formed of heterogeneous and microscopic areas of necrosis. so, the biopsy may represent a small part of the primary tumor and underestimate the tumor grading. 11C-methionine shows that are a useful biomarker in gliomas patients and has a higher sensitivity of detection and delineation of the tumor. In contrast with FDG-PET, 11C-methionine can detect tumors with (hypometabolism or is metabolism). 11C-methionine can be used as guidance during the biopsy process.[16] 11C-methionine shows a high uptake value in the pituitary gland and can distinguish between pituitary adenoma and other normal tissue in the brain. These increasing the reduction of GTV and the radiation dose to the normal tissue and the parotid glands, lacrimal glands and inner ears. The drawback of 11C-methionine it has a shorter half-life 20 min, also there is uptake values in other sites such as lacrimal glands, parotid glands, nasopharynx, bone marrow, and normal pituitary gland. [17]
11C-Choline can distinguish between curable diseases from metastatic diseases. [18]11C-Choline has been used for prostate cancer and contributed to choosing the best treatment strategy. 11C-Choline helps to improve the therapeutic ratio by high-precision radiation to the target and minimum dose to the normal tissue. It is not recommended using 11C-Choline in early diagnosis or tumor staging. The advantage of using 11C-Choline with prostate cancer that detects the target that localizes beyond the prostate bed so unnecessary radiation dose for prostate bed will be avoided.[19] 11C-Choline has sensitivity and specificity of 85%and 88% inpatient prostate-specific antigen (PSA). The limitation of 11C-Choline is cannot detect small lesions or low activity lesions. [20] other limitation of 11C-Choline cannot distinguish between tumor and non-tumor tissue in the prostate. [21]
Hypoxia traces have a great role in treatment planning provides a lot of information by Identify the resistant cells in the tumor. The target/background activity is less than FDG-PET. [10] Hypoxia traces is a nitroimidazole compound. [25] hypoxia tracer it is common to use in solid tumors such as head and neck squamous cell carcinomas (HNSCC). [26]
(18F-MISO) the first hypoxia PET tracer can increase the dose to hypoxic tumor up to 105Gy, can detect different tumor sites in one patient.[26]
(18F-FAZA) has the same uptake values and biodistribution as 18F-MISO, but the lower concentration in the tumor, that mean lower sensitivity in detection hypoxic sites.[26]
[25][27]
FDG-PET images have been used in brachytherapy for the cervix cancer patient. FDG-PET give significant information in 3D of the tumor or disease spread. The advantage from use FDG-PET image in treatment planning of cervix cancer patient is to reduce the dose to bladder and rectum due to the accurate dose coverage to the target volume. [28]
The new PET tracer FET has used in the detection of glioma and has excellent sensitivity and specificity improving the detection. also, have been used with Highly malignant or high-grade glioma. FET-PET used with MRI-based plans to shows the contrast. A mismatch between FET-PET and MRI-based in target volume contour, which improve treatment planning. Also, FET-FDG shows other sites that CT-based did not cover.[29] FET-PET id better than FDG-PET in the detection of a brain tumor but have the same performance in grade glioma. FET-PET mean, and maximum target/background ratio only can distinguish between tumor tissues and nontumor tissues. FET-PET helps to identify the tumor response to radiotherapy and delineation of target volume before radiotherapy which helps in estimating the effect of radiotherapy and chemotherapy in the tumor.[30]
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