Hybrid PET/CT

HYBRID PET/CT

Learning Objectives

  • What is a PET scan?
    • Positron Emission Tomography.
    • Non-invasive method of gaining 3D functional imaging.
    • Form of molecular imaging.
    • Can detect changes in tissues at a molecular level before structural changes are observed on anatomical imaging.
    • Indications include oncology, infection/inflammation, neurology, and cardiology.
  • Rationale of PET
    • Relies on administration of positron-emitting radiopharmaceuticals (β+\beta^+).
    • Radionuclides are bound to pharmaceuticals like FDG, DOTATATE, or PSMA to produce radiopharmaceuticals.
    • Examples of radiopharmaceuticals: 18F-FDG, 68Ga-PSMA, 68Ga-DOTATATE.
    • Accumulation of these radiopharmaceuticals varies:
      • 18F-FDG: areas with high glucose demand.
      • 68Ga-PSMA: areas expressing the PSMA receptor.
      • 68Ga-DOTATATE: areas expressing the somatostatin receptor.
    • More positrons emitted in a specific region result in more annihilation events, which leads to more gamma photons detected by the PET scanner, resulting in intense activity shown on the final PET image.
  • Physics behind PET imaging
    • Coincidence detection is the basis of PET imaging.
    • Photons detected at the same time are assumed to have originated along the line connecting the two detectors, known as the 'line of response' (LOR).
    • Compton interaction can occur where one or both photons are deflected but still reach detectors simultaneously, resulting in an inaccurate LOR and decreased image contrast.
    • Simultaneous but separate events are recorded as a true coincidence.

PET/CT Hybrid Imaging

  • Hybrid imaging is completed as a single study.
  • Advantages:
    • Co-registration of CT and PET data allows for anatomical localization and functional imaging.
    • Attenuation correction of PET data.
    • CT acquisition uses a tube voltage of 80 – 120 kVp.
    • mAs is variable, as CT can be used for:
      • Low dose (anatomical and attenuation correction purposes only).
      • Diagnostic quality.
  • Co-registration and Attenuation Correction
    • Co-registration: CT (anatomical and attenuation correction) + PET (functional) = PET/CT.
    • Attenuation correction:
      • Photons from deeper within the body are more likely to be absorbed by overlying tissues.
      • This diminishes the signal, hence the term 'attenuation'.
      • Correction is needed for a more accurate understanding of radiopharmaceutical distribution.
      • CT scan (or MRI for PET/MRI) is reconstructed into a map of attenuation coefficients.
      • The attenuation map is applied to PET data during the reconstruction process.
  • Standardised Uptake Values (SUV)
    • SUV allows for the quantification of radiopharmaceutical uptake in a region of interest.
    • It can be used to monitor the activity of a lesion over time; increased activity correlates with increased SUV.
    • Dependent on:
      • Radiopharmaceutical.
      • Dose or activity administered.
      • Body size (weight, BSA, or lean body mass).
      • Scanning equipment.
      • Uptake time.
  • Radiation Safety
    • 18F and 68Ga have short half-lives.
    • Patients are generally safe to leave after the scan and can continue with normal daily activities; activity is typically cleared within 24 hours.
    • Excess tracer is excreted via urine.
    • ALARA principle (Time, Distance, Shielding) is followed.

18F-FDG

  • What is it?
    • 18Fluorine (radioisotope) bound to FDG (Fluorodeoxyglucose).
    • Glucose analogue taken into cells and phosphorylated similarly to glucose.
    • Once phosphorylated, it cannot diffuse out and remains in cells but does not enter the glycolysis pathway.
    • Accumulates in areas of high metabolic demand (increased glucose needs), such as tumors, infection/inflammation, and active muscles.
  • Clinical Indications
    • Oncology: staging, restaging, evaluation of treatment response, radiation therapy planning, and locating primary tumor (breast, lung, colorectal, renal, pancreatic, melanoma, mesothelioma, head and neck).
    • Infection and inflammation: FUO, vasculitis, sarcoidosis.
    • Neurology: Alzheimer’s disease, frontotemporal dementia, epilepsy.
    • Cardiology: cardiac viability.
  • Patient preparation requirements
    • Fasting for 4 – 6 hours prior (plain water is okay).
    • Withhold diabetic medications (e.g., insulin, metformin).
    • Avoid strenuous exercise for 24 hours prior.
    • Establish IV access (18 or 20G if IV CT contrast is required; any size will do if IV contrast is not needed).
    • Measure blood glucose level (between 4 – 11mmol/L).
    • Measure height and weight.
    • Check patient history, including reason for PET/CT scan, recent surgeries, chemotherapy, immunotherapy or radiation therapy, any antibiotic or steroid medications, claustrophobia, incontinence issues, other imaging, and check for pregnancy and breastfeeding.
  • Dose
    • 185 – 444MBq of 18F-FDG, varying based on indication, PET/CT scanner, and acquisition time. Can be adjusted according to patient weight.
    • Administered intravenously, with automatic injectors available to reduce staff dose.
  • Uptake period
    • 18F-FDG is produced in a cyclotron.
    • Upon IV injection, 18F-FDG rapidly distributes throughout the body.
    • Cellular uptake increases and background activity decreases.
    • Primary route of clearance is through the kidneys and bladder.
    • Optimal imaging time is at 60 minutes due to maximum cellular uptake, background clearance, and physical half-life.
    • Quiet, dimly lit room and warm blanket to decrease brown fat uptake.
    • Patient should void prior to scan.
  • Variations to scanning
    • Oral contrast: highlight the bowel.
    • Lasix (Furosemide): dilute activity in the bladder.
    • Respiratory gating: to counteract respiratory motion in lungs, diaphragm, and liver.
    • Flat pallet: for radiation therapy planning.
  • Patient positioning
    • Supine, cushion under knees.
    • Arms above head if possible (unless head or neck indication).
    • Blanket for warmth (scan can take 15+ minutes).
    • Positioned using laser system.
  • Scan region
    • Varies due to clinical indication.
    • Most indications: vertex (or eyes) to mid-thighs.
    • Melanoma, FUO: vertex to toes.
    • Neurological indications: brain only.
    • Cardiac: cardiac view.
  • Scan process
    • Topogram (planning scan) to confirm scan region for PET and CT; used for CT dose modulation.
    • Low dose CT for anatomical localisation and attenuation correction. If required, diagnostic CT with IV contrast and breath-hold (some sites may perform diagnostic CT after PET scan).
    • PET scan (time varies with scanner, typically 10 – 20 min for vertex to mid-thigh) using continuous motion or bed positions. Patient breathes normally and is monitored with CCTV and speaker.
  • Normal image appearances
    • Brain: intense uptake.
    • Kidneys, ureters, and bladder: intense uptake.
    • Liver: moderate uptake.
    • Bone marrow: mild uptake.
    • Lungs: very mild to no uptake.
    • Variable uptake (intense, moderate, or mild uptake possible) in the bowel, muscle, heart, thyroid, laryngeal muscles, and tonsils.
  • Cardiac uptake
    • Varies from mild to intense, related to patient diet (carbohydrate and fat intake).
  • Brown fat
    • A type of adipose tissue with more mitochondria than white fat, more vascular, and higher oxygen usage.
    • Involved in non-shivering heat generation and regulating body temperature.
    • Activation occurs when cold, leading to increased FDG uptake.
    • More common in children but can be seen in adults.
  • Pathology and appearances
    • Lymphoma
    • Breast cancer
    • Liver metastases
    • Laryngeal Carcinoma for radiation therapy, highlighting biologically active tumor regions to improve targeting.
  • Case studies
    • FUO/Vasculitis – Longitudinal uptake along aorta and large vessels, pathognomonic for giant cell arteritis; treated with anti-inflammatory therapy.
    • FUO/Septic Arthritis – Pathological uptake at the right hip joint confirmed by biopsy and blood cultures as septic arthritis caused by Staphylococcus aureus; treated with prolonged i.v. antibiotic treatment.
  • Image variants and artefacts
    • Inadequate preparation: insulin, metformin, exercise.
    • Respiratory motion can cause mis-registration of activity in the lungs, liver, and diaphragm, reducing lesion detectability and affecting quantitation. Respiratory gating can be employed to correct for breathing motion.
    • Patient movement.
    • Physiological muscle uptake, e.g., chewing gum, strained neck, chronic cough.
    • Beam hardening

Prostate Specific Membrane Antigen (PSMA)

  • What is PSMA?
    • Transmembrane protein normally expressed in the epithelium of secretory ducts in benign prostate tissue.
    • Overexpressed 100 – 1000x more in malignant prostate cells.
    • Also expressed in lacrimal and salivary glands, kidneys, small intestine, liver, and spleen.
    • Expression is correlated with advanced disease, prostate-specific antigen level, and Gleason score.
    • Various radiopharmaceuticals are available for PSMA PET imaging, each with slightly different image appearances and pros vs. cons:
      • 68Ga-PSMA-11 (most common).
      • 68Ga-PSMA-I&T.
      • 18F-DCFPyL.
      • 18F-PSMA-1007.
  • Purpose of 68Ga-PSMA-11
    • Significantly influenced the diagnosis and management of prostate cancer; considered standard of care in Australia for diagnosis, staging, and monitoring therapeutic response.
  • Clinical indications
    • Primary staging in high-risk disease, where it's superior to CT, MRI, and bone scans for metastatic detection.
    • Localizing prostate cancer tissue in recurrent prostate cancer.
    • Evaluating PSMA expression for PSMA radionuclide therapy.
  • Patient preparation
    • No specific preparation is required.
    • Hydration.
    • Establish IV access.
    • Measure height and weight.
    • Allow patient to void before taking to uptake room.
    • Take patient history, including reason for PET/CT scan, recent surgeries, prostate biopsies, chemotherapy, hormone therapy, 177Lu-PSMA therapy, claustrophobia, incontinence issues, and other imaging.
  • Dose
    • 1.8 – 2.2 MBq/kg of 68Ga-PSMA-11 administered via manual intravenous injection. Can be prepared on-site in a generator due to its short half-life of 68 minutes, allowing for quick production, quality control, and injection.
  • Uptake period
    • Patient positioned on bed or recliner in uptake room; no requirement for patient to rest (can read, use phone).
    • Imaging commences at 60 minutes post-injection for good background clearance and increased activity in target tissue, compatible with the half-life of Gallium-68.
  • Additional interventions
    • Lesions close to bladder: administer Lasix (furosemide) prior to PSMA injection.
    • Delayed imaging up to 3 hours post-injection for improved contrast between target tissue and background activity and decreased uptake in the bladder.
  • Patient positioning
    • Instruct patient to empty bladder prior to scan, remove metal, position supine on scanner bed with arms up preferred, cushion under knees, and blanket for comfort.
  • Image acquisition
    • Scan region: vertex/eyes to mid-thigh. Pelvic protocol can be used with slower PET scan over pelvis or additional image over pelvis acquired to detect more photons and improve image quality.
    • Same image datasets as FDG PET: topogram, low dose or diagnostic CT, and PET emission scan.
  • Normal PSMA image appearances
    • Normal & variable physiological uptake in lacrimal, parotid, submandibular, and sublingual glands (intense); nasal mucosa and vocal cords (mild); liver (moderate); spleen (intense); small intestine/colon (mild to moderate); kidneys/bladder (intense).
  • Abnormal PSMA appearances
    • Any area of increased activity outside of normal regions should be assessed for symmetry, indicating pathologies such as local recurrence, bone metastases, and nodal disease.

68GA-DOTATATE

  • What is DOTATATE?
    • Binds to somatostatin receptors, commonly overexpressed on neuroendocrine tumors such as carcinoids, gastrinoma, insulinoma, pituitary tumors, paraganglioma, and pheochromocytoma.
  • Neuroendocrine tumors
    • Rare tumors that arise from neuroendocrine cells anywhere within the body, originating from endocrine glands (adrenal medulla, pituitary gland, parathyroid glands, endocrine islets (pancreas or thyroid)) or dispersed endocrine cells (lungs, GI tract); often slow-growing and well-differentiated.
  • Clinical indications
    • Localize primary tumors and detect sites of metastatic disease (staging).
    • Follow-up patients with known disease to detect residual, recurrent, or progressive disease (restaging).
    • Determine SST receptor status visually and by using SUV, as patients with SST receptors are more likely to respond to octreotide therapy.
    • Select patients with metastatic disease for SST receptor radionuclide therapy.
  • Patient preparation
    • Discontinue short-acting somatostatin analogues for 12 hours.
    • Schedule PET/CT scan 3 – 4 weeks after long-acting somatostatin analogue.
    • Hydration.
    • Establish IV access.
    • Measure height and weight.
    • Check pregnancy and breastfeeding.
    • Allow patient to void before taking to uptake room.
    • History, reason for PET/CT scan, any recent surgeries, biopsies, therapies including somatostatin analogue therapy, claustrophobia, incontinence issues, other imaging.
  • Dose
    • 2MBq/kg of body weight to a max of 200 MBq, produced in a generator onsite and administered via manual IV injection.
  • Uptake period
    • Patient positioned on bed or recliner in uptake room; no requirement for patient to rest (can read, use phone).
    • Shorter uptake period of 45 minutes compared to 18F-FDG and 68Ga-PSMA-11 due to quicker clearance from the bloodstream and reaching peak tumor uptake quicker.
  • Patient positioning
    • Instruct patient to empty bladder prior to scan, remove metal, position supine on scanner bed with arms up preferred, cushion under knees, and blanket for comfort.
  • Image acquisition
    • Scan region: vertex/eyes to mid-thigh.
    • Same image datasets as FDG PET: topogram, low dose or diagnostic CT, and PET emission.
  • Normal 68GA-DOTATE image appearances
    • Pituitary gland, salivary glands, spleen (intense), liver (moderate), kidneys/Bladder (moderate to intense).
  • Variable uptake
    • Adrenal gland, thyroid, salivary glands, stomach, and bowels.
  • Abnormal 68GA-DOTATE appearances – pathologies
    • Paraganglioma
    • Pancreatic NET, including with liver metastases.

18FDG vs 68GA-DOTATE

  • Most NETs are well-differentiated and express somatostatin receptors; however, some NETs are poorly differentiated and more aggressive.
  • A combination of 18F-FDG and 68Ga-DOTATATE imaging can be used to evaluate the molecular profile of the disease.

Paediatrics

  • PET/CT scans can be performed in paediatric patients using 18F-FDG (for oncology or neurological indications like epilepsy) or 68Ga-DOTATATE (for oncology, specifically NETs); 68Ga-PSMA-11 is rarely used.
  • Both radiopharmaceutical and CT doses are reduced in paediatric patients based on weight.
  • Normal Paediatrics image appearances for 18F-FDG and 68GA-DOTATE (as covered in presentation only).
  • Patient Preparation is the same as discussed for each radiopharmaceutical, with additional considerations for the age of the patient and their ability to remain still (sedation or general anaesthetic may be required).
  • Image appearances for 18F-FDG
    • Thymus uptake.
    • Epiphyseal plates of long bones.
    • Increased likelihood of brown fat.
    • Increased laryngeal muscles if talking or crying.
  • Image appearances for 68Ga-DOTATATE
    • Epiphyseal plates of long bones.
    • No other paediatric-specific image appearances

PET CT for RT planning

  • PET/CT scans provide invaluable information regarding the molecular behavior of a tumor, combining anatomical/functional imaging to improve differentiation between viable tumor and adjacent structures.
  • Highlights functional changes before structural or morphological changes are evident on anatomical imaging, which can lead to modified tumor volumes.
  • Appearance - Image delineation of disease using PET/CT
  • Limitations
    • Requires precise registration of PET/CT to planning CT (use of flat pallet, tattoos, and laser may assist).
    • Respiratory gating for thoracic tumours.
    • No standard for the display of intensity thresholds on PET/CT imaging, which can lead to variations in the overall size appearance of tumors.
    • Operator-dependent contouring.