18F-Fluciclovine [Axumin®] PET/CT Scan

A ¹⁸F-Fluciclovine [Axumin®] is a nuclear medicine study using positron emission tomography (PET) with computed tomography (CT) to localize recurrent disease in patients who were previously treated for prostate cancer and are now presenting with an increased prostate-specific antigen (PSA). ¹⁸F-Fluciclovine is a synthetic amino acid analog. Amino acids are the building blocks of proteins used by cells for growth and metabolism. In prostate cancer cells, the need for amino acids is elevated. Therefore, the uptake of ¹⁸F-Fluciclovine will be high in prostate cancer cells and low in normal cells. In 2016, the ¹⁸F-Fluciclovine PET/CT exam was approved by the US Food and Drug Administration (FDA) to evaluate patients with suspected recurrent prostate cancer.

The greatest strength of ¹⁸F-Fluciclovine PET/CT is localizing small metastatic lymph nodes. Its performance was significantly better than a traditional CT scan. ¹⁸F-Fluciclovine PET/CT was found to assist clinicians in choosing the treatment management for their patients with suspected recurrent disease. In some cases, the detection of small metastatic lymph nodes may change the treatment plan to include surgery or radiation.

A ¹⁸F-Fluciclovine PET/CT nuclear exam may be positive when other exams are negative. The higher the prostate-specific antigen (PSA) level, the higher the chance of the scan to be positive.  Yet, ¹⁸F-Fluciclovine PET scans were reported to be positive in patients with PSA as low as 0.2 ng/ml. For bone lesions, ¹⁸F-Fluciclovine may demonstrate intense activity in lesions that cannot be well seen on CT images (small marrow replacing or lytic lesions) but may show no uptake in lesions that appear dense on CT images (sclerotic lesions). Therefore, a bone scan or MRI may be needed when the ¹⁸F-Fluciclovine PET is negative, but the CT demonstrates a suspicious sclerotic lesion. 

The FDA recently approved newer PSMA based PET tracers (¹⁸F- DCFPyL [Pylarify] and ⁶⁸Ga-PSMA-11) for clinical use in patients with prostate cancer.  PSMA tracers bind to the extracellular portion of the prostate-specific membrane antigen (PSMA), which is over-expressed in prostate cancer cells. The main PSMA tracer widely available in the United States is ¹⁸F-DCFPyL or PyL (PYLARIFY®, piflufolastat F-18). Both Pylarify and PSMA-11 PET tracers have broader indications than ¹⁸F-Fluciclovine and can be offered for patients with primary and suspected prostate cancer recurrence. ¹⁸F-Fluciclovine can be provided only for patients with suspected prostate cancer recurrence. ⁶⁸Ga-PSMA-11 tracer demonstrated superiority over ¹⁸F-Fluciclovine in evaluating small lymph nodes when PSA was lower than 2 ng/mL but was inferior to ¹⁸F-Fluciclovine  for the localization of recurrent disease in the prostate and prostate bed regardless of PSA level. Although ¹⁸F-Fluciclovine  and ¹⁸F-DCFPyL have not been directly compared it is believed that ¹⁸F-DCFPyL tracer has a relatively similar performance compared to that of ⁶⁸Ga-PSMA-11 tracer.

¹⁸F-Fluciclovine and PSMA PET tracers have different mechanisms of uptake and localization. With the growing knowledge and experience of detecting prostate cancer using PET/CT scans, we believe that with time PSMA based tracers will be used primarily to evaluate patients with prostate cancer, and ¹⁸F-Fluciclovine will be used as an adjunct to answer specific clinical questions. 

Figure 1. ¹⁸F-Fluciclovine PET/CT scan in patients who found to have less than 1 cm metastatic lymph nodes (high uptake of ¹⁸F-Fluciclovine).  Based on CT criteria, less than 1 cm lymph nodes considered to be normal (not cancer).  Image A: Uptake in a 5 mm pelvic pre-sacral lymph node.  The patient was planned to undergo whole pelvis radiation therapy.  Due to the ¹⁸F-Fluciclovine PET/CT scan, the radiation zone decreased to cover only the lymph node area.  The PSA level went back to zero.  Images B, C, D:  Unexpected presentation of normal-sized lymph nodes outside of the pelvic (B, C: higher abdomen, D: chest), highly specific for metastatic disease.  Conventional whole pelvic radiation therapy (if was given) would have been failed.

Figure 2.  Images A, B: ¹⁸F-Fluciclovine PET/CT scan demonstrates intense uptake in lytic bone lesions.  Images C,D: ¹⁸F-Fluciclovine PET/CT scan demonstrates no uptake in a suspicious sclerotic lesion.  Therefore, ¹⁸F-Fluciclovine PET/CT scan cannot replace bone scintigraphy, such as Tc99m-MDP or F18-NaF bone scans.