Ofer Shamni

Purpose: Quaternary ammonium salts have demonstrated marked accumulation in the left ventricular (LV) myocardium of rodents and swine. To investigate the mechanism underlying this uptake, the present study examined the interaction of [¹⁸F]fluoroethylquinolinium ([¹⁸F]FEtQ) with the family of organic cation transporters (OCTs). Procedures: The cellular uptake of [¹⁸F]FEtQ into HEK293 cells, expressing human OCT1, -2, or -3 (HEK293-hOCT), and its inhibition by corticosterone was evaluated in vitro. The inhibitory effect of decynium 22 (D 22) in vivo was also studied, using PET/CT of HEK293-hOCT tumor-bearing mice. Furthermore, the distribution kinetics of [¹⁸F]FEtQ were determined in rats, with and without pre-administration of corticosterone, and following administration to a non-human primate (NHP). Results: The accumulation of [¹⁸F]FEtQ in HEK293-hOCT cells was 15–20-fold higher than in control cells and could be inhibited by corticosterone. in vivo, the uptake of [¹⁸F]FEtQ in the LV myocardium of corticosterone-treated rats was significantly reduced compared to that of untreated animals. Similarly, following administration of D 22 to HEK293-hOCT tumor-bearing mice, the peak tumor uptake of [¹⁸F]FEtQ was reduced by 40–45 % compared to baseline. Contrary to the distinct accumulation of [¹⁸F]FEtQ in the LV myocardium of rats, no cardiac uptake was observed following its administration to a NHP. Conclusions: The quinolinium salt derivative [¹⁸F]FEtQ interacts with the family of OCTs, and this interaction could account, at least in part, for the increased uptake in the LV myocardium of rodents. Nonetheless, its low affinity for hOCT3 and the results of PET/CT imaging in a NHP indicate a limited clinical applicability as a radiopharmaceutical for cardiac and/or OCT imaging.

We previously presented the radiolabeled ammonium salt [¹¹C]-dimethyl diphenylammonium trifluoromethanesulfonate ([¹¹C]DMDPA) as a potential novel PET-MPI agent. The current study aimed to increase the clinical applicability of PET-MPI by designing and synthesizing fluorinated ammonium salt derivatives. Four fluorinated DMDPA derivatives and two quinolinium salt analogs were radiolabeled. The dynamic distribution in vivo, following injection of each derivative into male SD rats, was evaluated using small-animal dedicated PET/CT. Organ uptake after injection of [¹⁸F]fluoroethylquinolinium acetate ([¹⁸F]FEtQ) was examined ex vivo. Four fluorinated DMDPA derivatives were synthesized, two were labeled with fluorine-18: [¹⁸F]fluoroethyl-methyldiphenylammonium trifluoromethanesulfonate ([¹⁸F]FEMDPA) and [¹⁸F]fluorobuthyl-methyldiphenylammonium trifluoromethanesulfonate ([¹⁸F]FBMDPA). The other two were labeled using carbon-11: [¹¹C]methyl-(3-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([¹¹C]3-F-DMDPA) and [¹¹C]methyl-(4-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([¹¹C]4-F-DMDPA). All four DMDPA derivatives exhibited significantly lower heart/liver radioactivity uptake ratios (0.6, 0.4, 0.7 and 0.6, respectively) compared to that of [¹¹C]DMDPA (1.2). Conversely, the two radiolabeled quinolinium salt derivatives, [¹¹C]methylquinolinium iodide ([¹¹C]MeQ) and [¹⁸F]FEtQ demonstrated improved heart/liver ratios (2.0 and 1.3, respectively) with clear visualization of the left ventricle myocardium. Renal clearance was the major route of elimination. Among the fluorinated quaternary ammonium salts tested, [¹⁸F]FEtQ yielded the best images. Further studies are in progress to elucidate the underlying mechanism of its cardiac uptake.

Background: [¹⁸F]-Fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) may sometimes be suboptimal for imaging gastric adenocarcinoma. The recently introduced [⁶⁸Ga]Ga-FAPI-04 (FAPI) PET/CT targets tumor stroma and has shown considerable potential in evaluating the extent of disease in a variety of tumors. Methods: We performed a head-to-head prospective comparison of FAPI and FDG PET/CT in the same group of 13 patients with gastric adenocarcinoma who presented for either initial staging (n = 10) or restaging (n = 3) of disease. Lesion detection and maximum standardized uptake value (SUV_max) were compared between the two types of radiotracers. Results: All ten primary gastric tumors were FAPI-positive (100% detection rate), whereas only five were also FDG-positive (50%). SUV_max was not significantly different, but the tumor-to-background ratio was higher for FAPI (mean, median, and range of 4.5, 3.2, and 0.8–9.7 for FDG and 12.9, 11.9, and 2.2–23.9 for FAPI, P = 0.007). The level of detection of regional lymph node involvement was comparable. FAPI showed a superior detection rate for peritoneal carcinomatosis (100% vs. none). Two patients with widespread peritoneal carcinomatosis underwent a follow-up FAPI scan after chemotherapy: one showed partial remission and the other showed progressive disease. Conclusions: The findings of this pilot study suggest that FAPI PET/CT outperforms FDG PET/CT in detecting both primary gastric adenocarcinoma and peritoneal carcinomatosis from gastric cancer. FAPI PET/CT also shows promise for monitoring response to treatment in patients with peritoneal carcinomatosis from gastric cancer; however, larger trials are needed to validate these preliminary findings.

Radiolabeled prostate‐specific membrane antigen (PSMA) targeting PET‐tracers have become desirable radiopharmaceuticals for the imaging of prostate cancer (PC). Recently, the PET radiotracer [¹⁸F]PSMA‐1007 was introduced as an alternative to [⁶⁸Ga]Ga‐PSMA‐11, for staging and diagnosing biochemically recurrent PC. We incorporated a one‐step procedure for [¹⁸F]PSMA‐1007 radiosynthesis, using both Synthra RNplus and GE TRACERlab FxFN automated modules, in accordance with the recently described radiolabeling procedure. Although the adapted [¹⁸F]PSMA‐1007 synthesis resulted in repeatable radiochemical yields (55 ± 5%, NDC), suboptimal radiochemical purities of 87 ± 8% were obtained using both modules. As described here, modifications made to the radiolabeling and the solid‐phase extraction purification steps reduced synthesis time to 32 minutes and improved radiochemical purity to 96.10%, using both modules, without shearing the radiochemical yield.