On site production of [18F]PSMA-1007 using different [18F]fluoride activities: practical, technical and economical impact

Abstract

Background Prostate-specific membrane antigen is overexpressed in prostate cancer and it is considered a good target for positron emission tomography/computed tomography imaging of primary cancer and recurrent/metastatic disease, as well as for radioligand therapy. Different PSMA-analogues labeled with [68Ga]gallium have been investigated, showing excellent imaging properties; however, only small amounts can be produced for each radiolabeling. Recently, a [18F]fluoride labeled PSMA-inhibitor, [18F]PSMA-1007, has been introduced, and it has ensured large-scale productions, overcoming this limitation of [68Ga]PSMAs. In this study, PSMA-1007 has been labeled with low (A), medium (B) and high (C) starting activities of [18F]fluoride, in order to verify if radiochemical yield, radiochemical purity and stability of [18F]PSMA-1007 were affected. These parameters have been measured in sixty-five consecutive batches. In addition, the estimation of [18F]PSMA-1007 production costs is provided. Results The radiochemical yield for low and medium activities of [18F]fluoride was 52%, while for the high one it decreased to 40%. The radiochemical purity was 99% for all three activities. [18F]PSMA-1007 did not show radiolysis up to 8 h after the end of synthesis, confirming that the radiopharmaceutical is stable and suitable to perform diagnostic studies in humans for a long period of time after the end of radiolabeling. Furthermore, radiochemical stability was demonstrated in fetal bovine serum at 4 °C and 37 °C for 120′. Conclusions A starting activity of [18F]fluoride of 90 GBq (B) seems to be the best option enabling a final amount of about of 50 GBq of [18F]PSMA-1007, which is promising as it allows to: (a) perform a large number of scans, and/or (b) supply the radiopharmaceutical to any peripheral diagnostic centers in need.

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer

“…The cost of each single PET/CT exam considered a standard dose of 259 MBq for [ 18 F]PSMA-1007 and of 154 MBq for [ 68 Ga]Ga-PSMA-11. For [ 18 F]PSMA-1007 the presented range of starting activity is the most cost/effective, as previously shown[6].…”

“…Conversely, the limit of low starting activity does not apply to the production of fluorinated PSMA inhibitors. The starting activity range of [ 18 F]Fluoride plays a key role in the final yield for [ 18 F]PSMA-1007; thus, the optimization of the variables influencing the yields of the synthesis is mandatory as we have previously demonstrated [6]. In fact, using different starting activities of [ 18 F]Fluoride: low (55.91 ± 6.69 GBq), medium (89.06 ± 4.02 GBq), and high (162.38 ± 6.46 GBq), we found that the medium one was the most compliant for clinical needs, ensuring the best match of RCY, costs, and number of performed PET/CT exams [6].…”

“…The labeling procedure, quality controls, and cost of production for preparing [ 18 F]PSMA-1007 in our institution have been analyzed and published [6]. Considering a starting activity of about 90 GBq of [ 18 F]Fluoride, a final activity of 45-50 GBq of [ 18 F]PSMA-1007 was obtained, allowing 25-30 PET/CT exams per day.…”

“…Finally, we evaluated the cost of production, the amount of the final product along with the number of allowed PET/CT exams. To evaluate the costs of production of [ 68 Ga]Ga-PSMA-11 and [ 18 F]PSMA-1007 in a nuclear medicine center with its own cyclotron/radiopharmacy facility, we adopted the same procedure previously published for [ 18 F]PSMA-1007 [6]. The knowledge obtained from all of these data will support the choice of the best option to adopt in a nuclear medicine center.…”

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [18F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

“…Although the half-life of 68 Ge/ 68 Ga generators is 271 days, they can offer a maximum activity of 1.85 GBq for 68 Ga, and they can only scan in a limited number of prostate cancer patients . For a higher number of patients in several PET centers with the characterization of 18 F, 18 F-labeled diagnostic radiopharmaceuticals targeting PSMA have several advantages. , An on-site cyclotron produces large-scale 18 F without several productions, and 18 F has a longer half-life (109.8 min) and lower positron energy (0.65 MeV, 96.7% β + ), which increases the theoretical maximum spatial resolution. , …”