Molecular imaging is the visual representation of biological processes that take place at the cellular or molecular level in living organisms. To date, molecular imaging plays an important role in the transition from conventional medical practice to precision medicine. Among all imaging modalities, positron emission tomography (PET) has great advantages in sensitivity and the ability to obtain absolute imaging quantification after corrections for photon attenuation and scattering. Due to the ability to label a host of unique molecules of biological interest, including endogenous, naturally occurring substrates and drug-like compounds, the role of PET has been well established in the field of molecular imaging. In this article, we provide an overview of the recent advances in the development of PET radiopharmaceuticals and their clinical applications in oncology.

Prostate cancer is the most common cancer to affect men in the United States and the second most common cancer in men worldwide. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging is gradually recognized as a novel technique that can improve treatment decisions and affect clinical care of prostate cancer patients as the PSMA expression in most prostate malignant cells correlates well with serum prostate-specific antigen concentration. Initial development of PSMA-targeted radiopharmaceuticals is based on monoclonal antibodies such as ProstaScint™; however, because small molecules are advantageous due to faster blood clearance and better tumor permeability, the focus of current investigative efforts is therefore switched to developing PSMA inhibitor-based radiopharmaceuticals, as they are typically small molecular agents. To date, several ⁶⁸Ga and ¹⁸F-labeled PSMA-targeted molecules have shown promising results in patients with biochemical recurrent prostate cancer using PET/computed tomography (CT). Studies of these PSMA-targeted radiopharmaceuticals also suggest a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and methylene diphosphonate bone scan) or ¹¹C/¹⁸F-choline PET/CT. In addition, the tracers based on PSMA-617 and PSMA I&T can be labeled with α and β⁻ emitters (e.g., ²²⁵Ac, ⁹⁰Y, and ¹⁷⁷Lu) as well and serve as a theranostic tool for patients with metastatic prostate cancer. While the clinical impact of such concept remains to be verified, the preliminary results of PSMA molecular radiotherapy are very encouraging. With these in mind, the aim of this article is to provide an overview of the recent advancement of PSMA-targeted radiopharmaceuticals and their clinical applications.

Background (S)-4-(3-¹⁸F-Fluoropropyl)-L-Glutamic Acid ([¹⁸F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc-), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of ([¹⁸F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [¹⁸F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [¹⁸F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [¹⁸F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use. Results Starting with activity levels of 60–85 GBq, the fully-automated process to produce [¹⁸F]FSPG took less than 45 minutes with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were > 95% and the formulated [¹⁸F]FSPG solution was determined to be sterile and colorless with the pH of 6.5–7.5. No radiolysis of the product was observed up to 8 hours after final batch formulation. Conclusions In summary, cGMP-compliant radiosyntheses and quality control of [¹⁸F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [¹⁸F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [¹⁸F]FSPG.