Are two PET radiotracers better than one?

There seem to be clinical trials of new PET radiotracers for the detection of prostate cancer all the time. In addition to the FDA-approved C-11 Choline, NaF18, FDG, and fluciclovine PET scans, most of the new PET scans target the PSMA protein on prostate cancer cells. On the horizon, we have seen some encouraging reports on PET radiotracers that target the Gastrin Releasing Peptide Receptor (GRPR) with a peptide called bombesin. GRPR, as the name implies, is ubiquitous in the stomach and intestines, but seems to show up in several different kinds of cancer cells as well.

Zhang et al. reported the results of a very small pilot study using a synthetic molecule that targets two different receptor proteins at the same time (also see this link). One part of the molecule (bombesin - BBN) targets the GRPR protein. The other part, called RGD, targets a protein called αvβ3. αvβ3 is a member of a family of proteins called integrins. These proteins are responsible for maintaining the structural integrity of cells. αvβ3 promotes cell adhesion, spreading and blood supply -- qualities vital to metastatic progression.

They used both the single Ga-68-BBN PET/CT and the dual Ga-68-BBN-RGD PET/CT to detect prostate cancer among 13 patients (4 newly diagnosed, 9 recurrent) with biopsy-proven prostate cancer. The dual PET radiotracer found cancer:

• In the prostates of 3 of the 4 men with newly diagnosed prostate cancer vs. 2 of the 4 men using the BBN-only radiotracer.
• 14 metastatic lymph nodes vs. 5 metastatic lymph nodes using the BBN-only radiotracer.
• 20 bone metastases vs. 12 metastatic bone metastases using the BBN-only radiotracer.

There were no toxic reactions.

While encouraging, it is still very early to draw conclusions. There is no confirmation that the extra "metastases" discovered were indeed metastases - they may be false positives. And there are no clues as to which kinds of prostate cancer the dual PET radiotracer is sensitive to, and which kinds are undetectable.

If confirmed by larger studies, it may be possible to not just detect the cancer, but to kill the detectable cancer cells as well with beta emitters like Lu-177 or alpha emitters like Ac-225.