By: Dan Sperling, MD

 This is the third in a series of five articles about PET scans and their application in prostate cancer.

As explained in the first article in this series, Positron Emission Tomography (PET) scan depends on tumor cells taking up radioactive isotopes bonded to molecules that the cells need for their growth. These radiopharmaceuticals are called radiotracers or simply tracers. The most common tracer for many organ-based tumors is FDG (fluorodeoxyglucose); however, prostate cancer (PCa) does not absorb this tracer as well as other types of tumors.

A different radiotracer called Carbon-11 Acetate (C-11 acetate) shows great promise as a way to detect early metastatic PCa before treatment, and also recurrent PCa after treatment. Like the tracer choline C-11, discussed in the previous article, C-11 acetate is drawn to prostate cancer cells. C-11 acetate is quickly and selectively taken up by the membranes of PCa tumor cells whether they are located in the gland, prostate bed, lymph nodes or distant organs. Within minutes after injection into a vein, the concentrated radioactivity in any site is detectable by PET or PET/CT scans. The entire scanning process usually takes less than 20 minutes from the time of injection.

Both C-11 acetate and choline C-11 have a relatively short half-life, meaning the radioactivity level quickly diminishes. Thus, they require onsite production at imaging centers that are large enough to afford a cyclotron, the sophisticated technology needed to isolate the atomic ions and generate molecular bonds to create the radiotracer. No time must be wasted from production, to transport to the imaging equipment, to injection.

Both tracers are often used with a process called PET/CT scan. CT (Computerized Tomography) clearly shows anatomical structures, whereas PET lights up abnormally functioning tissue. When the two types of imaging are done together at the same time and “fused,” called PET/CT scans, tumors are seen in their precise anatomical soft tissue locations (prostate gland, prostate bed, lymph nodes, other organs such as liver or lung) though less effective for PCa in the bone.

There are two differences between C-11 acetate and choline C-11:

• C-11 acetate is not yet approved by the FDA for detection of prostate cancer, so it is still being investigated in a small number of clinical trials.
• Though investigational, C-11 acetate appears to outperform choline C-11, though not hugely.

Detecting recurrence

The early research done with C-11 acetate was limited to detecting recurrent prostate cancer in hopes that it would prove superior to the traditional standard of “biochemical recurrence” or rising PSA. Traditionally, treatment by radical prostatectomy (surgical prostate removal or simply RP) was considered to have failed if PSA reached 0.2 ng/mL in two consecutive blood tests; after radiation, failure was defined as a PSA of 2.0 ng/mL above nadir (lowest point). Needless to say, PSA tells nothing about the location or extent of treatment failure. The problem with conventional imaging such as CT scan is that it does not identify recurrence until a suspicious mass reaches a relatively large size. Based on PSA alone, many patients were place on hormones (chemical castration) to deprive the tumor of testosterone which was believed to fuel its growth. Yet many of these patients might be eligible for a potentially curative treatment of a localized tumor if it could be identified before it metastasized to other organs, at which point the average expected survival is 5 years. The importance of early recurrence detection cannot be overstated.

Indeed, it was soon evident that C-11 acetate PET/CT performed well at highlighting recurrent PCa. Tissue samples drawn from needle biopsy or surgical removal of lymph glands showed a very high degree of correspondence between the imaging and the lab analysis, thus confirming the extent of PCa recurrence. Based on this confirmation, a strategy for managing the recurrence could be developed.

Planning primary treatment

More recently, studies are being done to determine the value of C-11 acetate PET/CT prior to primary treatment in order to rule in or out very early metastasis. Put another way, if a patient being considered for RP could be shown to have disease extension into the prostate bed, or at least one positive lymph node based on such imaging, it could make a difference in the treatment plan by adding a course of radiation. A spot of cancer in the liver or lung would eliminate RP and instead suggest a systemic treatment.

Monitoring response to systemic treatment

Another potential use for C-11 acetate PET/CT is to monitor how well hormone therapy is controlling the spread of PCa. Finally, this type of scan is under study to explore cancer changes when chemotherapy is administered as a treatment for hormone-resistant metastatic PCa.

Patients interested in finding a clinical trial in their area can search http://clinicaltrials.gov/ct2/show/NCT01304485?term=c+11+acetate+PET+prostate+cancer&rank=3

The next article will discuss the statistical evidence upon which the current and future value of PET/CT scanning for prostate cancer is based.