Radiopharmaceuticals and Imaging Techniques

Radiopharmaceuticals and PET/CT Imaging

Prostate Cancer

  • Fluorine-18 fluciclovine (Axumin)

    • Used for prostate cancer recurrence.

    • FDA Approval: May 2016 (Blue Earth Diagnostics).

    • Recurrence Statistics: Up to a third of men treated for prostate cancer will experience recurrence.

  • Limitations of Conventional Imaging:

    • CT (Computed Tomography) and Bone Scintigraphy (Bone Scan) are unable to identify the site of recurrence until PSA (Prostate-Specific Antigen) levels rise to between 10-20 ng/ml.

    • Importance of identifying the recurrence site for secondary treatment selection.

    • F-18 FDG (Fluorodeoxyglucose) PET has limited utility until patients develop castration-resistant disease, where physiological uptake can be obscured by the bladder.

Prostate Fluciclovine Mechanism

  • Mechanism of Action:

    • Fluciclovine is a synthetic amino acid that is taken up by amino acid transporters in tissues, specifically ASCT2 and LAT1.

    • These transporters facilitate the uptake of amino acids like glutamine and leucine into cells for protein synthesis, cell growth, and metabolism.

Clinical Example

  • Case Study:

    • 61-year-old male, PSA 0.4 ng/ml post robotic-assisted laparoscopic prostatectomy.

    • Detected an 8 mm lymph node proximal to the rectal wall.

    • Radiotherapy was not advised; the patient received hormonal therapy.

    • Note: Bone Scans and CT require a PSA level of 10-20 ng/ml for effective imaging.

Diagnostic Performance Study (Emory University)

Agent

Location

Sensitivity

Specificity

Accuracy

PPV

NPV

Fluciclovine F-18 (n=91)

Prostate/bed

90.2%

40.0%

73.6%

75.3%

66.7%

ProstaScint (n=91)

Prostate/bed

67.2%

56.7%

63.7%

75.9%

45.9%

Fluciclovine F-18 (n=70)

Extra-prostatic sites

55.0%

96.7%

72.9%

95.7%

61.7%

ProstaScint (n=70)

Extra-prostatic sites

10.0%

86.7%

42.9%

50.0%

41.9%

Prostate C-11 Choline

  • Indication:

    • Also used for the recurrence of prostate cancer.

    • Limitations:

    • Requires a cyclotron due to its 20-minute half-life.

    • 511 keV emission.

    • Choline, a nutrient rapidly consumed by tumor cells.

    • Has been used to identify ectopic or hard to find parathyroid adenomas.

  • Comparison:

    • Effective as an imaging agent but is now being replaced by PSMA agents.

Prostate PSMA Agents

  • F-18 piflufolastat (Pylarify)

    • Manufacturer: Lantheus (TruVu Latest).

    • FDA Approval: 2021.

    • Dosage: 8-10 mCi.

    • Imaging begins 60 minutes post-injection, not exceeding 90 minutes.

    • No fasting required prior to the procedure.

    • Patient hydration is advised.

    • Scan time: 12 to 40 minutes depending on the number of bed positions and time allocated per bed.

  • Ga-68 Gozetotide (Illucix, Locametz):

    • Additional PSMA agent utilized for imaging.

    • Manufacturer details: Illucix - Telix, Locametz - Novartis Pharmaceuticals.

    • Dose: 3-7 mCi.

    • Patient prep involves hydration.

    • Imaging conducted 50 to 100 minutes post-injection, covering from skull to thighs.

  • Ga-68 Illucix (PSMA)

    • Patient preparation includes hydration and avoiding exercise for 24 hours prior to the injection.

    • Dosage: 3-7 mCi.

    • Imaging occurs 50 to 100 minutes post-injection, covering from skull to thigh.

    • Recent release: Gozellix.

Oncology Breast

  • Fluorine-18 fluoroestradiol (Cerianna):

    • Indicated for ER-positive breast cancer.

    • FDA Approval: 2020.

    • Invasive lobular carcinoma comprises up to 15% of all breast cancer cases.

    • Notable for atypical metastatic spread and diffuse growth patterns with fewer calcifications.

    • **Comparison Study **

    • 18F-FES PET/CT detected more metastatic lesions than 18F-FDG PET/CT.

  • Imaging Guidelines:

    • Recommended dose range: 3-6 mCi.

    • Imaging should occur 80 minutes post-injection and prior to endocrine therapies targeting ER modulators and ER down-regulators, focusing on the skull to thighs.

Neuroendocrine Imaging

  • Gallium-68 DOTATATE (Netspot):

    • FDA Approval: 2016.

    • Recommended Dose: 0.54 mCi/kg, max dose 5.4 mCi.

    • Imaging conducted 40-90 minutes post-injection.

    • Half-life: 67.8 minutes.

    • Mechanism: Ga-68 dotatate binds to somatostatin receptors, particularly with the highest affinity for subtype 2 (SSTR2).

    • Patient preparation includes hydration.

  • Cu-64 Dotatate (Detectnet):

    • Half-life: 12.7 hours.

    • FDA Approval: 2020.

    • Recommended Dose: 4 mCi.

    • Imaging should occur 45-90 minutes post-injection.

    • Patient preparation considerations:

    • For patients on long-acting somatostatin analogs, a wash-out period of 28 days prior to imaging is recommended.

    • For those on short-acting somatostatin analogs, a 2-day washout period is required before imaging.

Neurology Imaging

  • Fluorine-18 florbetapir (Amyvid):

    • FDA Approval: 2012.

    • Indicated for PET imaging of the brain to evaluate the density of amyloid beta neuritic plaques in adults with cognitive impairment.

    • Uses: Evaluating Alzheimer's disease (AD) and other causes of cognitive decline.

    • Selection of patients for amyloid beta-directed therapy is detailed in the therapeutic product prescribing information.

  • Recommended Dose: 10 mCi; Imaging should occur 30-50 minutes post-injection with a scan time of about 10 minutes.

  • Limitations:

    • A positive Amyvid scan does not conclusively diagnose AD or other cognitive disorders.

    • The test has not been established for predicting dementia development or other neurological conditions.

  • Fluorine-18 fluorbetaben (Neuraceq):

    • FDA Approval: 2014.

    • Evaluates beta-amyloid plaque density.

    • Recommended Dose: 8.1 mCi.

    • Imaging performed 45-130 minutes post-injection, with a scan length of 15-20 minutes.

    • Patient preparation includes hydration.

  • Fluorine-18 flutemetamol (Vizamyl):

    • FDA Approval: 2013.

    • Used to estimate beta-amyloid neuritic plaque density in cognitive impairment cases.

    • Recommended Dose: 5 mCi.

    • Imaging 60-120 minutes post-injection with a scan length of 10-20 minutes.

Cardiology Imaging

  • Fluorine-18 flurpiridaz (Flyrcado):

    • Approved for myocardial perfusion imaging for coronary artery disease (CAD) as of September 2024.

    • Half-life: 110 minutes.

    • Significance: PET is the most effective form of myocardial perfusion imaging for detecting CAD, without the need for an onsite mobile generator or cyclotron.

    • Dosage Recommendations: Rest dose of 2.5-3 mCi, stress dose of 6-6.5 mCi, with an option for exercise stress set at 9-10 mCi.

    • Recommended dose should be two-fold higher for rest versus stress pharmacological imaging.

    • A three-fold higher rest dose compared to stress is suggested for exercise stress.

  • Minimum Time Between Doses:

    • 30 minutes when administering pharmacologic stress.

    • 60 minutes when administering exercise stress.

  • Image Acquisition Protocol:

    • Rest imaging should begin 5 minutes after Flyrcado administration, capturing images for 10 minutes in 3D mode.

    • Pharmacologic stress imaging should begin 5 minutes post-administration and should also be captured for 10 minutes in 3D mode.

    • For exercise stress imaging, acquisition should commence 15-25 minutes post-Flyrcado administration.