PSMA PET-CT

Prostate specific membrane antigen (PSMA) PET-CT shows prostate cancer cells by binding a radiolabelled ligand to the PSMA protein on their surface. PSMA is expressed at low levels in normal prostate tissue and at high levels in most prostate cancers, with expression rising with grade and in castration resistant disease.

Gallium-68 PSMA-11 (gozetotide) is used in many centres at a dose of about 2 MBq for each kg (150 to 250 MBq), and fluorine-18 agents (piflufolastat, PSMA-1007) at about 250 to 350 MBq.

Images are taken 45 to 90 minutes after injection (60 to 120 minutes for fluorine-18 agents), from the vertex or skull base to the mid-thigh, with a low dose CT.

The effective dose is about 3 to 7 mSv for the tracer plus the CT. Prostate cancer is the commonest cancer in men in many countries, and the second cause of cancer death.

PSMA PET-CT is more sensitive than CT, MRI and bone scan for nodal and bone metastases, with a sensitivity of about 80 to 90% and a specificity over 95% for staging in high risk disease, and it identifies recurrence at low levels of prostate specific antigen (PSA).

Indications.

• Primary staging of men with intermediate and high risk prostate cancer before curative treatment.
• Biochemical recurrence after prostatectomy (PSA rising to 0.2 ng/mL or more, confirmed) or after radiotherapy (PSA 2 ng/mL over the lowest value).
• Planning of salvage radiotherapy or focal treatment by finding the site of recurrence.
• Restaging of metastatic disease, and assessment of response in selected men.
• Selection for PSMA-targeted radioligand treatment (lutetium-177 PSMA) in castration resistant disease.
• Biopsy targeting in men with negative MRI and persistent suspicion.
• Other PSMA-avid tumours (renal cell, hepatocellular, thyroid, glioma) are a research use.

Not for routine use in low risk disease, or for screening.

Contraindications and precautions.

• Pregnancy and breast feeding do not arise, since the test is used in men.
• Allergy is rare.
• Hydration and voiding before the scan reduce the dose and the activity in the bladder. A diuretic (furosemide) may be given for gallium-68 agents to clear the ureters and bladder.
• Androgen deprivation lowers PSMA expression early, and may raise it later. Treatment is noted and, if possible, the scan is timed before starting or changing treatment.
• No fasting is needed.
• Metal in the hip (prosthesis) causes artefact next to the prostate bed.
• The patient must lie still for 20 to 30 minutes.

Preparation and technique.

The patient drinks water and empties the bladder before the injection and before imaging. The tracer is injected, and the patient rests for 45 to 90 minutes. Furosemide 20 mg may be given.

The CT is taken first, then the PET acquisition from the head or skull base to the mid-thigh. A pelvic acquisition after voiding, or delayed imaging, is used when the bladder hides the prostate bed. MRI of the pelvis with PET (PET-MRI) improves local assessment.

Reporting records the number and site of lesions in the prostate, nodes, bone and viscera, with the intensity of uptake compared with the liver and the salivary glands. The relation to the prostate bed, pelvic and retroperitoneal nodes is stated.

Normal appearances.

Physiological uptake is high in the salivary and lacrimal glands, kidneys and ureters, spleen and bowel (especially small bowel), moderate in the liver, and lower in the bone marrow, muscle and lung. Nerve ganglia (coeliac, sacral, cervical) show mild focal uptake. The bladder contains tracer activity.

Interpretation.

• Primary tumour: focal uptake in the prostate, usually in the area with a high MRI score. The uptake correlates with grade, but a low uptake does not exclude tumour. The scan is not a substitute for MRI and biopsy for the primary.
• Nodal metastases: pelvic and retroperitoneal nodes with uptake, even when under 8 mm in size. Detection is much better than with CT.
• Bone metastases: focal uptake in marrow, often before changes on CT and bone scan. Bone disease may be seen in the spine, ribs, pelvis and long bones.
• Visceral metastases: lung, liver and adrenal lesions, less common.
• Biochemical recurrence: detection depends on the PSA level. It is about 40 to 50% at a PSA under 0.5 ng/mL, 55 to 70% at 0.5 to 1, 75 to 85% at 1 to 2, and 90% or more over 2 ng/mL. Sites are local (prostate bed), nodal, bone or distant.
• Oligometastatic disease: 1 to 5 lesions, which may be treated with directed radiotherapy or surgery.
• Treatment selection: lesions with uptake greater than the liver, with no large PSMA-negative lesions seen on fluorodeoxyglucose PET or CT, are suitable for lutetium-177 PSMA treatment.
• Response: fall in uptake and number of lesions, together with PSA.
• Pitfalls of benign uptake: ganglia, Paget disease, healing rib fractures, haemangioma, fibrous dysplasia, degenerative bone disease, and other tumours (renal, thyroid, breast, lung).

Critical values and findings needing immediate action.

• Spinal metastasis with cord compression: high dose dexamethasone, urgent MRI and oncology or surgical review.
• Impending pathological fracture: orthopaedic review and radiotherapy.
• Bladder outlet obstruction, hydronephrosis or renal failure from nodal or pelvic disease: urgent urological decompression.
• Extensive visceral disease with symptoms: urgent oncology review.

Limitations and artefacts.

• Bladder activity hides local recurrence in the prostate bed. Voiding, diuretics, delayed images and PET-MRI help.
• Fluorine-18 PSMA-1007 has less urinary excretion but more liver and bowel uptake and more benign bone uptake.
• Benign lesions take up the tracer and cause false positives (ganglia, bone lesions, inflammation, other tumours). Correlation with CT and clinical course is needed.
• Neuroendocrine differentiation and some dedifferentiated tumours are PSMA-negative. Fluorodeoxyglucose PET or somatostatin receptor imaging may show them.
• Small lesions and very low PSA levels give false negative results.
• Treatment with androgen deprivation changes expression, and the timing of the scan relative to treatment affects detection.
• Interpretation varies between readers, and structured reporting with experienced readers is preferred.
• Local availability, access and cost limit use.
• The effect of the scan on long term outcomes is still being studied, and treatment decisions should be made in a multidisciplinary meeting.

Special groups.

• Men with high risk disease: staging before surgery or radiotherapy.
• Men with rising PSA after treatment: early localisation of recurrence.
• Men on androgen deprivation: note the treatment and expect variable uptake.
• Men with hip prostheses: artefact near the prostate bed. Use PET-MRI or delayed images.
• Men with renal failure: bladder activity and kidney uptake are altered, and imaging is still possible.
• Women: not used.
• Regions: prostate cancer presents at advanced stage, and PSMA PET-CT is available in very few centres. Bone scan, CT, MRI and PSA are used.

Follow up tests.

• Multiparametric MRI of the prostate and targeted biopsy.
• Bone scan, CT or whole body MRI if PSMA PET-CT is not available.
• Fluorodeoxyglucose PET-CT for aggressive or PSMA-negative disease.
• PSA kinetics, testosterone, alkaline phosphatase, lactate dehydrogenase and renal function.
• Biopsy of a suspicious lesion for histology.
• Genetic testing in selected men.
• Referral to urology, oncology, radiation oncology or nuclear medicine.