Flotufolastat F 18 (Posluma): The Silicon-Fluoride Prostate Scan Tracer and Its Two Trials

What it is

Posluma is a diagnostic injection, and flotufolastat F 18 is the molecule in it that does the work. Its target is PSMA (prostate-specific membrane antigen), which sits on the surface of most prostate cancer cells in quantity. Where the molecule collects, its fluorine-18 atom gives a signal a PET scanner can map.

Its label does not call it a peptide. The word does not appear anywhere in the Posluma label. The label gives a long chemical name and three plain facts about the structure:

• the molecular weight is 1537.3;
• the molecule includes a ring called DOTAGA that holds a non-radioactive gallium atom;
• the radioactive fluorine-18 is bound to a silicon atom.

That makes it more than three times the size of piflufolastat F 18, the other fluorine-18 PSMA tracer in this library. It appears here because readers meet it next to gozetotide, a PSMA tracer whose own label does use the word peptide.

How it works

The label states that flotufolastat F 18 binds to PSMA on cells, including prostate cancer cells, and is taken inside them. Fluorine-18 gives off positrons that a PET scanner detects. Fluorine-18 has a physical half-life of 109.8 minutes.

After injection the tracer spreads to the liver (15.8% of the dose), the blood in the heart (7.4%) and the kidneys (3.2%). It leaves in the urine: about 7% of the dose in the first 2 hours and about 15% by 4.5 hours.

What the two trials found

Two single-arm trials support the label. Every scan was read separately by three central readers kept blind to the patient's clinical details.

Reading the LIGHTHOUSE row. In that trial, about 24% of the men had cancer in their pelvic lymph nodes on pathology. Take reader 1: the scan found 21 of those men and missed 49. A positive scan was right in 57–70% of men, depending on the reader, and a negative scan in about four of five.

In SPOTLIGHT, at least one reader saw a positive spot in 366 of 389 men (94%). That figure is not a measure of accuracy, and the label says so: it counts true and false positives together. Roughly half of the positive regions were confirmed by pathology or other imaging.

The readers often disagreed

The label reports something most summaries leave out. In SPOTLIGHT, the three readers agreed on whether each of five body regions was positive or negative in only 118 of 389 patients (30%). The agreement score (Fleiss kappa) was 0.41.

The warnings section draws the consequence. It says interpretation "may differ depending on imaging readers, particularly in the prostate/prostate bed region", and suggests a team discussion and tissue confirmation when a treatment decision depends on the scan.

Reactions recorded in the label

Across 747 men given a single injection, the label records diarrhea in 5 (0.7%), a rise in blood pressure in 4 (0.5%) and injection site pain in 3 (0.4%). Its two warnings are about misread images and added radiation.

What is not established

• Neither result is proof: per the label, a clear image does not exclude prostate cancer and a positive one does not establish it.
• The label says the effect of hormone-blocking treatment on the scan's performance "has not been established".
• In SPOTLIGHT, negative scans were not checked against a reference standard, so the trial cannot say how many cancers were missed.
• This entry does not compare flotufolastat with other PSMA tracers. The trials above did not test one against another, and the label itself cautions against comparing side-effect rates across trials.

Where it stands

Related reading

PSMA is also the target of a treatment, the lutetium-carrying ligand in Pluvicto. Outside prostate cancer there is the somatostatin-receptor imaging peptide.