OBJECTIVE The purpose of this article is to summarize advances in PET fluorescence resolution, agent design, and preclinical imaging that make a growing case for clinical PET fluorescence imaging. CONCLUSION Existing SPECT, PET, fluorescence, and MRI contrast imaging techniques are already deeply integrated into the management of cancer, from initial diagnosis to the observation and management of metastases. Combined positron-emitting fluorescent contrast agents can convey new or substantial benefits that improve on these proven clinical contrast agents.

[18/19F]-4, an anionic GCPII/PSMA inhibitor for image-guided intervention in prostate cancer, is described. [19F]-4 is radiolabeled with a radiochemical yield that is ≥27% and a molar activity of 190 ± 50 mCi/μmol in a <1 h, one-step, aqueous isotopic exchange reaction. [19F]-4 allows PSMA expression to be imaged by fluorescence (FL) and [18F]-PET. PC3-PIP (PSMA-positive, EC50 = 6.74 ± 1.33 nM) cancers are specifically delineated in mice that bear 3 million (18 mg) PC3-PIP and PC3 (control, PSMA-negative) cells. Colocalization of [18/19F]-4 PET, fluorescence, scintillated biodistribution, and PSMA expression are observed.

Fluorescein is modified to bear 18F so that it can act as both a positron emitter, and a fluorophore, allowing detection by positron emission tomography (PET), scintillation, and fluorescent imaging (FL). [18F]-2 is injected into the intrathecal space of rats and used to observe the cerebrospinal fluid (CSF) that bathes the brain and spine. Injury in three different applications is visualized with [18F]-2: 1) detection of a 0.7 mm paranasal-sinus CSF leak (CSFL); 2) detection of 0.5 mm puncture damage to the thoracic spine (acute spinal cord injury); and 3) detection of intracerebral hemorrhage/edema because of traumatic brain injury. In all models, the location of injury is visualized with [18F]-2 at high resolution. [18F]-2 PET imaging may be a superior alternative to current clinical contrast myelography and 131I, 111In or 99mTc radionuclide cisternography. Like fluorescein, [18F]-2 may also have other uses in diagnostic or fluorescence guided medicine.