Background: Boron neutron capture therapy (BNCT) is a molecular radiation treatment based on the ¹⁰B (n, α) ⁷Li nuclear reaction in cancer cells, in which delivery of ¹⁰B by 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is of critical importance. The PET tracer 4-borono-2-¹⁸ F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. However, because of the difference in chemical structure between BPA-fr and FBPA and the difference in the dose administered between BPA-fr (therapeutic dose) and FBPA (tracer dose), the predictive value of FBPA PET for BPA-fr accumulation in the tumor and normal tissues is not yet clearly proven. We conducted this study to validate FBPA PET as a useful test to predict the accumulation of BPA-fr in the tumor and normal tissues before BNCT. Methods: RGC-6 rat glioma cells (1.9 × 10⁷) were implanted subcutaneously in seven male F344 rats. On day 20 after the tumor implantation, dynamic PET scan was performed on four rats after injection of FBPA for 1 h. Whole-body PET/CT was performed 1 h after intravenous injection of the FBPA solution (30.5 ± 0.7 MBq, 1.69 ± 1.21 mg/kg). PET accumulation of FBPA in the tumor tissue and various normal tissues was estimated as a percentage of the injected dose per gram (%ID/g). One hour after the PET/CT scan, BPA-fructose (167.32 ± 18.65 mg/kg) was injected intravenously, and the rats were dissected 1 h after the BPA-fr injection. The absolute concentration of ¹⁰B in the autopsied tissues and blood was measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Results: The highest absolute concentration of ¹⁰B determined by ICP-OES was found in the kidney (4.34 ± 0.84 %ID/g), followed by the pancreas (2.73 ± 0.63 %ID/g), and the tumor (1.44 ± 0.44 %ID/g). A significant positive correlation was found between the accumulation levels of BPA-fr and FBPA (r = 0.91, p < 0.05). Conclusions: FBPA PET can reliably predict accumulation of BPA-fr in the tumor as well as normal tissues.

Background: Fibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [¹⁸F]AlF-FAPI-74 is a positron emission tomography tracer with high selectivity for FAP, which has already shown high accumulation within human tumors in clinical studies. However, [¹⁸F]AlF-FAPI-74 radiosynthesis has not been optimized using an automated synthesizer. Herein, we report a one-pot and one-step automated radiosynthesis method using a multi purpose synthesizer. Results: Radiosynthesis of [¹⁸F]AlF-FAPI-74 was performed using a cassette-type multi purpose synthesizer CFN-MPS200. After the recovery rate of trapped [¹⁸F]fluoride onto the anion-exchange cartridge using a small amount of eluent was investigated manually, a dedicated [¹⁸F]AlF-FAPI-74 synthesis cassette and synthesis program for one-pot and one-step fluorination was developed. The solutions for the formulation of [¹⁸F]AlF-FAPI-74 synthesized using this were evaluated to obtain stable radiochemical purity. The recovery rate of [¹⁸F]fluoride with only 300 µL of eluent ranged 90 ± 9% by introduction from the male side and elution from the female side of the cartridge. In automated synthesis, the eluted [¹⁸F]fluoride and precursor solution containing aluminum chloride were mixed; then, fluorination was performed in a one-pot and one-step process at room temperature for 5 min, followed by 15 min at 95 °C. As a result, the radioactivity of [¹⁸F]AlF-FAPI-74 was 11.3 ± 1.1 GBq at the end of synthesis from 32 to 40 GBq of [¹⁸F]fluoride, and its radiochemical yield was 37 ± 4% (n = 10). The radiochemical purity at the end of the synthesis was ≥ 97% for all formulation solutions. When the diluent was saline, the radiochemical purity markedly decreased after 4 h of synthesis. In contrast, with phosphate-buffered saline (pH 7.4) or 10 mM phosphate-buffered saline (pH 6.7) containing 100 mg of sodium ascorbate, the radiochemical purity was stable at 97%. Non-radioactive AlF-FAPI-74 and total impurities, including non-radioactive AlF-FAPI-74, were 0.3 ± 0.1 µg/mL and 2.8 ± 0.6 µg/mL. Ethanol concentration and residual DMSO were 5.5 ± 0.2% and 21 ± 6 ppm, respectively. Conclusions: We established a one-pot one-step automated synthesis method using a CFN-MPS200 synthesizer that provided high radioactivity and stable radiochemical purity for possible clinical applications.

[11C]methionine (MET) has been used to monitor amino acid metabolism in tumors, the pancreas, liver, and myocardium. The aim of the present study was to standardize [11C]MET positron emission tomography (PET) by optimizing the timing of initiation of the scan and applying correction to the plasma concentrations of neutral amino acids (NAAs), where necessary.

Background: [¹⁸F]PSMA-1007, a positron emission tomography (PET) tracer, specifically targets prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer. PSMA-PET is effective especially for regional detection of biochemical recurrence, which significantly affects patient management. Herein, we established and optimized a one-step radiolabeling protocol to separate and purify [¹⁸F]PSMA-1007 with a CFN-MPS200 synthesizer for clinical application. Results: A dedicated single use cassette and synthesis program for [¹⁸F]PSMA-1007 was generated using a single-step method for direct precursor radiolabeling. In the cassette, three tube types (fluoro-elastomer, PharMed® BPT, silicone) and two different precursor salts (trifluoroacetic acid or acetic acid) were compared for optimization. Furthermore, three-lot tests were performed under optimized conditions for quality confirmation. Activity yields and mean radiochemical purity of [¹⁸F]PSMA-1007 were > 5000 MBq and 95%, respectively, at the end of synthesis, and the decay-corrected mean radiochemical yield from all three cassettes was approximately 40% using a trifluoroacetic acid salt precursor. Fluoro-elastomer tubings significantly increased the amount of non-radioactive PSMA-1007 (8.5 ± 3.1 μg/mL) compared to those with other tubings (0.3 μg/mL). This reduced the molar activity of [¹⁸F]PSMA-1007 synthesized in the cassette assembled by fluoro-elastomer tubings (46 GBq/μmol) compared to that with PharMed® BPT and silicone tubings (1184 and 1411 GBq/μmol, respectively). Residual tetrabutylammonium, acetonitrile, and dimethyl sulfoxide levels were < 2.6 μg/mL, < 8 ppm, and < 11 ppm, respectively, and ethanol content was 8.0–8.1% in all three cassettes and two different salts. Higher activity yields, radiochemical purities, and decay-corrected radiochemical yields were obtained using an acetic acid salt precursor rather than a trifluoroacetic acid salt precursor (7906 ± 1216 MBq, 97% ± 0%, and 56% ± 4%). In the three-lot tests under conditions optimized with silicone cassettes and acetic acid salt precursor, all quality items passed the specifications required for human use. Conclusions: We successfully automated the production of [¹⁸F]PSMA-1007 for clinical use and optimized synthesis procedures with a CFN-MPS200 synthesizer using a silicone cassette and acetic acid salt precursor. Cassette availability will facilitate a wide spread use of [¹⁸F]PSMA-1007-PET, leading to an effective prostate cancer management.

Purpose 4-Borono-2-[¹⁸F]fluoro-l-phenylalanine ([¹⁸F]FBPA) synthesized with [¹⁸F]F₂, produced using the ¹⁸O(p, n)¹⁸F reaction, has been reported for increasing radioactivity. However, a dedicated system and complex procedure is required to reuse the costly [¹⁸O]O₂ gas; also, the use of [¹⁸F]F₂ as a labeling agent reduces the labeling rate and radiochemical purity. We developed a stable and practical method for [¹⁸F]FBPA synthesis by combining [¹⁸F]F₂, produced using a [¹⁸O]O₂ single-use system, and a [¹⁸F]CH₃COOF labeling agent. Methods The produced [¹⁸F]F₂ was optimized, and then [¹⁸F]FBPA was synthesized. For passivation of the target box, 0.5% F₂ was pre-irradiated in argon. Gaseous products were discarded; the target box was filled with [¹⁸O]O₂ gas, and then irradiated (first irradiation). Then, the [¹⁸O]O₂ gas was discarded, 0.05–0.08% F₂ in argon was fed into the target box, and it was again irradiated (second irradiation). The [¹⁸F]F₂ obtained after this was passed through a CH₃COONa column, converting it into the [¹⁸F]CH₃COOF labeling agent, which was then used for [¹⁸F]FBPA synthesis. Results The mean amount of as-obtained [¹⁸F]F₂ was 55.0 ± 3.3 GBq and that of as-obtained [¹⁸F]CH₃COOF was 21.6 ± 1.4 GBq after the bombardment. The radioactivity and the radiochemical yield based on [¹⁸F]F₂ of [¹⁸F]FBPA were 4.72 ± 0.34 GBq and 12.2 ± 0.1%, respectively. The radiochemical purity and molar activity were 99.3 ± 0.1% and 231 ± 22 GBq/mmol, respectively. Conclusion We developed a method for [¹⁸F]FBPA production, which is more stable and practical compared with the method using [¹⁸O]O₂ gas-recycling and [¹⁸F]F₂ labeling agent.

Tumor blood flow (TBF) is related to drug delivery and hypoxia, both of which can impact the efficacy of anti-cancer therapies. Although integrin α_vβ₃ expression is related to tumor angiogenesis, it remains unclear whether the degree of angiogenesis affects TBF. This study aimed to evaluate the expression of integrin α_vβ₃ in mouse tumor models using [⁶⁸Ga]Ga-DOTA-c(RGDfK) peptide positron emission tomography (PET) and immunohistochemical staining. PET studies were conducted using mouse C6 glioma models and MIA PaCa-2 (n = 6 each). The [⁶⁸Ga]Ga-DOTA-c(RGDfK) peptide was injected via the tail vein (2.17 ± 0.28 MBq), and 10 min static PET scans were performed. Immunohistochemical analysis was conducted using an integrin α_Vβ₃ antibody. [⁶⁸Ga]Ga-DOTA-c(RGDfK) peptide PET revealed higher uptake of the radiotracer in C6 gliomas than in MIA PaCa-2 tumors. The mean standardized uptake value was significantly higher in C6 gliomas (0.35 ± 0.058) than in MIA PaCa-2 tumors (0.17 ± 0.045). Histological analysis revealed intense integrin α_Vβ₃ expression in the C6 gliomas, whereas the MIA PaCa-2 tumors had low expression levels. This study showed that the expression of integrin α_vβ₃ can be differentiated by the [⁶⁸Ga]Ga-DOTA-c(RGDfK) peptide, suggesting the potential applicability of this peptide in the evaluation of the relationship between angiogenesis and TBF.