Detection of prostate cancer and its recurrence is challenging as it is a heterogeneous disease and methods such as PET imaging and measurement of biochemical response using prostate specific membrane antigen (PSMA) shows poor specificity and sensitivity. PSMA is a transmembrane protein having 750 amino acids.
In normal prostate tissue, PSMA is in the apical epithelium of secretory ducts, while in malignant tissues, PSMA moves to the luminal surface of the ducts and is also overexpressed 100 to 1000-fold, which is not seen in benign prostate disease. Hence, PSMA is a great agent for targeted imaging and therapy planning.
A modern diagnostic procedure, gallium Ga 68-labeled PSMA-11 positron emission tomography/computer tomography (Ga68-PSMA-PET/CT) imaging has become a gold standard in the diagnosis of prostate cancer. Ga-68 PSMA binds to prostate tumor cells and can be then be imaged using the PET technique. This technique also helps monitor prostate cancer metastasis and recurrence even at low levels of PSA.
Prostate cancer cells, 3D illustration. Image Credit: Kateryna Kon / Shutterstock
Studies on Ga68-PSMA PET Technique
Several studies have shown that Gallium Ga 68-labeled PSMA-11 PET/CT imaging is very effective in diagnosing prostate cancer patients and also helps track rise in PSMA post treatment. A study evaluating 336 Ga68-PSMA PET scans from 262 patients with prostate cancer found that the technique helped detect extra-prostatic disease in 53.2% of patients before starting treatment. Ga68-PSMA showed 95% sensitivity with histopathological diagnosis and 66.7% sensitivity with biochemical response. Its positive predictive value was 98%. Ga68-PSMA imaging helped detect disease progression / castration resistance in all the 26 (100%) patients who had surgical castration. This proved that Ga68-PSMA imaging has excellent sensitivity in diagnosis, staging and restaging, analyzing response to therapy, and prognostication in patients with prostate cancer.
Ga68-PSMA-PET/CT also performs better than other PET techniques usually used for prostate cancer detection, even at low PSA. PSMA is over expressed in more than 90% of all prostate cancers and they can be accurately detected by this molecular imaging technique. It is said to be superior to magnetic resonance imaging (MRI) in the detection of metastasis in prostate cancer.
It can reliably predict the stage of prostate cancer and thus help guide an appropriate treatment approach. 68Ga-PSMA PET/CT also can carry out a guiding biopsy that boosts sampling accuracy, and also guide radiotherapy and surgery. It also helps determine which patients might benefit from targeted radionuclide therapy.
PSMA PET-CT: A disruptive technology in the management of prostate cancer
Advantages of Ga68-PSMA-11 Imaging
Ga68-PSMA-11 has a high affinity to LNCaP cell membrane receptors resulting in high PET/CT detectability at low cell concentrations in a mixed population of cells. 68Ga-labeled diagnostic radiopharmaceuticals can be easily synthesized on site with the help a 68Ge/68Ga generator. 68Ga-PSMA PET/CT has been proved to be superior to MRI and choline-based PET/CT imaging. This technique has been shown to be more effective than bone scintigraphy in the assessment of potential bone metastases. Ga68-PSMA PET/CT helps stage prostate cancer and then modify management plan in one-fifth of all patients studied.
Treatment re-planning substantially improves prognosis. Serial 68Ga-PSMA PET/CT imaging can be used to determine radiotherapy outcomes in recurrent nodal disease and also plays a key role in post-definitive radiotherapy in the detection of the site of biochemical relapse. It has the potential to guide treatment and facilitate prostate biopsies of higher accuracy. The Ga68-PSMA PET/CT imaging is also being tested as a way to monitor therapeutic response to cancer treatment modalities.
Limitations of 68Ga-PSMA PET/CT Imaging
The limitations of this novel technique have not been sufficiently explored mainly due to the lack of a good technique to compare it at low levels of PSMA and also due to the dearth of studies focusing on its limitations at the microscopic stage. Although PET cameras usually have high sensitivity, at very low levels of cellular concentration, the biological / pharmacological behavior of the Ga68-PSMA tracer affects tumor imaging. Some studies have shown that detection limits of Ga68-PSMA-11-PET/CT decreases with increase in living cells. This is due to the partial volume effects as well as the background activity in the sample being tested.
The advent of new tracers combined with the use of PET/CT imaging is paving way for improved early diagnosis as well as focused treatment and management of patients with prostate cancer.
Reviewed by Deepthi Sathyajith, MPharm
Further Reading
Prostate cancer vaccines: Progress, challenges, and future directions