Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT for diagnosis of metastatic lesions in patients with recurrent papillary thyroid carcinoma.

OBJECTIVE: We aimed to evaluate the gallium-68-labeled fibroblast-activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in localizing papillary thyroid carcinoma (PTC) foci in patients with biochemical relapse. Papillary thyroid carcinoma has achieved biochemical recovery after appropriate treatment and had biochemical relapse in the last follow-up were included in this retrospective study. Gallium-68-FAPI and fluorine-18-fluorodeoxyglucose (68F-FDG) PET/CT were performed to detect recurrence foci. SUBJECTS AND METHODS: Biochemically relapsed patients who underwent total thyroidectomy and were diagnosed with pathologically differentiated thyroid cancer were included in our study. Gallium-68-FAPI and 18F-FDG PET/CT imaging methods were used to determine the focus of metastasis or recurrence in all patients. RESULTS: Among 29 patients enrolled to the study, pathological subgroups were papillary (n=26) and poorly differentiated (n=3) PTC. Anti-thyroglobulin (TG) antibody positivity were noted in 5 of the patients, while all 29 of them were TG positive and had been consist of three groups as follows: 2-10ng/mL (n=4), 11-300ng/mL (n=14), 301ng/mL and above (n=11). Recurrence was detected in 72.4% (n=21) and 86% (n=25) of the patients via 18F-FDG and 68Ga-FAPI, respectively. Accuracy of detection noted as 100% (5/5), 75% (3/4), and 92.9% (13/14) in groups with the anti-TG antibody positivity, TG levels of 2-10ng/mL and 11-300ng/mL, respectively, when the two imaging modalities were utilized together. Furthermore, accuracy of 68Ga-FAPI was 100% (11/11) in the group with TG levels of 301ng/mL and above, whereas accuracy of 18F-FDG was 81.8% (9/11). Lastly, median maximum standardized uptake value (SUVmax) of recurrent lesions detected by the 68Ga-FAPI (median SUVmax: 6.0) were statistically higher than the ones detected by the 18F-FDG (median SUVmax: 3.7) (P=0.002). CONCLUSION: In recurrent PTC especially in case of higher TG levels, 68Ga-FAPI can be used in patients with inconclusive 18F-FDG findings.

A practical fully automated radiosynthesis of [18F]Flurpiridaz on the module modular lab-pharmtracer without external purification.

BACKGROUND: [18F]Flurpiridaz is a promising novel cardiac PET imaging tracer formed by the radiolabeling of pyridaben derivative with fluorine-18. Clinical studies on [18F]Flurpiridaz are currently at the phase III level for the assessment of MPI. Providing high image quality thanks to its relatively long half-life, F-18 is a high-potential radionuclide for the early detection of CAD. In this study, we aimed to develop a fully automated synthesis of [18F]Flurpiridaz without further preparative HPLC purification. RESULTS: Precursor 6 was obtained by multi-step synthesis starting from mucochloric acid (1) as a sole product with 35% yield and identified by spectroscopic measurement. Manually cold labeling experiments were performed using the stable isotope [19F]F, and TBA-HCO3 PTC provided desirable fluorinated compound with high yield. A fully automated [18F]Flurpiridaz synthesis on the ML-PT device provided 55-65% radiochemical yield with more than 98% radiochemical purity. The final product purification method demonstrated that [18F]Flurpiridaz could be obtained without an external preparative HPLC system as a pharmaceutical quality. CONCLUSION: A novel and fascinating strategy was developed for the fully automated synthesis of [18F]Flurpiridaz (7) on ML PT. Organic synthesis of precursor 6 was achieved with a desirable yield and characterized by NMR and HR-MS. A detailed set of cold experiments were completed for optimization conditions before hot trials and TBA-HCO3 increased molar activity with a minimum amount of side products. Radiolabeling showed that our self-designed automated synthesis method enables high radiochemical yield and radiochemical purity for the production of [18F]Flurpiridaz. The desirable radiopharmaceutical quality of the product was obtained without using an additional preparative HPLC system. [18F]Flurpiridaz (7) preserved its stability within 12 h and final specifications were consistent with the acceptance criteria in Ph. Eur. regulations.

Novel developed HPLC analyses of [68 Ga]Ga/[177 Lu]Lu-EDTMP and [68 Ga]Ga/[177 Lu]Lu-DOTA-Zoledronate.

Radiolabeled phosphonates have found widespread applications in nuclear medicine for the treatment of bone metastases. Even though considerable attention has been devoted to the administration of radiolabeled phosphonates to the patients, quality control (QC) studies belong to detection of them are still speculative and need to be improved. Herein, practical, efficient, and more reliable high-performance liquid chromatograpy (HPLC) methods were described for the first time. Radiochemical purity was easily determined by our developed analytical methods. N,N-Dimethylhexylamine and N,N-dimethyltetradecylamine were furnished as suitable ion pair reagents for the identification of radiopharmaceutical products. Effects of column type, pH of the mobile phase, and salt concentration were also examined.

Comparison of 68Ga-FAPI PET/CT and 18FDG PET/CT Modalities in Gastrointestinal System Malignancies with Peritoneal Involvement.

PURPOSE: In this study, we aimed to investigate the utilization of 68Ga-FAPI PET/CT in comparison to 18FDG PET/CT to evaluate the peritoneal involvement of the gastrointestinal malignancies alongside primary lesions and other metastatic foci. PROCEDURES: A total of 37 patients with various gastrointestinal malignancies with accompanying peritoneal involvement who underwent 68Ga-FAPI PET/CT and 18FDG PET/CT imaging between September 2020 and June 2021 were included in this retrospective study. SUVmax values of 68Ga-FAPI and 18FDG were compared according to lesion locations. Also, the lesion localization ability of both imaging was compared in patient basis. RESULTS: Of the 37 patients with peritoneal involvement (23 males and 14 females; median age, 62.8 ± 12.7 years), 35.1% (n = 13) had colorectal cancer, 37.8% (n = 14) gastric cancer, and 27.0% (n = 10) pancreaticobiliary cancer. While 45.9% of them were operated, the remaining did not have surgery. The mean time interval between two studies was 3.2 days (range: 2-6 days). The mean SUVmax value of peritoneal metastases (p < 0.001) was significantly higher with 68Ga-FAPI PET/CT compared to that with 18FDG PET/CT, as in primary lesions (p < 0.001), lymph node metastases (p = 0.006), liver metastases (p = 0.002), and bone metastases (p = 0.018). A total of 185 lesions was detected in the initial assessment with 18FDG PET/CT. Of the total lesions detected with 18FDG PET/CT, 5 of them were evaluated as benign lesions with 68Ga-FAPI PET/CT also in accordance with the reference standard. In addition to 180 lesions detected with 18FDG PET/CT, a total of 37 additional malignant lesions, 12 of which were peritoneal metastases, were detected with 68Ga-FAPI PET/CT. CONCLUSION: 68Ga-FAPI PET/CT was determined to be superior to 18FDG PET/CT in terms of detection of peritoneal involvement with high image quality as well as primary tumor and other metastatic foci. Consequently, 68Ga-FAPI PET/CT can be used as a complementary imaging modality especially for inconclusive 18FDG findings due to the lack of accuracy of 18FDG PET/CT in some of the metastatic regions, especially in the liver.

Comparison of [68Ga]-FAPI PET/CT and [18F]-FDG PET/CT in Multiple Myeloma: Clinical Experience.

OBJECTIVE: In this study, we aimed to compare [68Ga]FAPI PET/CT and [18F]FDG PET/CT imaging to detect lesions in multiple myeloma. METHODS: A total of 14 patients with multiple myeloma who underwent [68Ga]FAPI PET/CT and [18F]FDG PET/CT imaging were included in this retrospective study. SUVmax values of [68Ga]FAPI and [18F]FDG were compared according to lesion locations. Also, lesion localization ability of both imaging methods was compared on the patient basis. RESULTS: In 4 of 14 patients, [68Ga]FAPI PET/CT and [18F]FDG PET/CT have not detected any bone lesions. In 8 of the remaining 10 patients [18F]FDG PET/CT detected bone lesions but in this group, 6 patients showed more higher SUVmax values than [18F]FDG PET/CT in [68Ga]FAPI PET/CT.In contrast, 2 of 8 patients showed more higher SUVmax values than [68Ga]FAPI PET/CT in [18F]FDG PET/CT. Moreover, [68Ga]FAPI PET/CT detected bone lesions in two patients, which werenot detected by [18F]FDG PET/CT. Also, in five patients, [68Ga]FAPI PET/CT showed more bone lesions in comparison with[18F]FDG PET/CT. Only one patient, [18F]FDG PET/CT showed more bone lesions. Three extramedullary involvements were observed in the following locations: lung, presacral lymph node, and soft tissue mass lateral to the right maxillary sinus. Among these involvements, higher SUVmax values were observed in the lung and presacral lymph node with [68Ga]FAPI compared to [18F]FDG. However, the soft tissue mass showed a higher SUVmax value in [18F]FDG than [68Ga]FAPI. CONCLUSIONS: No significant superiority was observed in [68Ga]FAPI PET/CT over [18F]FDG PET/CT in patients with MM. However, [68Ga]FAPI PET/CT can be utilized as a complementary imaging method to [18F]FDG PET/CT in some settings, especially in low-[18F]FDG affinity and inconclusive cases. Considering the favorable aspects of [68Ga]FAPI PET/CT in MM, such as low background activity, absence of non-specific bone marrow, and physiological brain involvement, further studies with a larger sample size should be conducted.

Detailed Chemistry Studies of 225Actinium Labeled Radiopharmaceuticals.

BACKGROUND: The synthesis of 225Actinium derivatives was afforded by using PSMA- 617, DOTATATE peptides, and EDTMP ligand. Detailed experiments, quality control (QC), and stability studies were also well described. The radiolabelling reactions were performed in mild conditions with desirable radiochemical yields and high radiochemical purities. METHODS: PSMA-617, DOTATATE were radiolabelled with 225Actinium in 0.1 M HCl in the presence of ascorbate buffer solution and passed through the C-18 light cartridge for purification and the product was eluted by ethanol-water solution. EDTMP was also radiolabelled with 225Actinium without using any stabilizer and purification step. All products were well analyzed by R-TLC and R-HPLC. The stability of those compounds was also studied within the validity period of time. RESULTS: 225Ac-DOTATATE and 225Ac-PSMA-617 were obtained at the same condition. The radiochemical yield of 225Ac-DOTATATE was less than225Ac-PSMA 617. The stability experiments indicating decay daughters of 225Actinium appeared after T0 +1 h due to the recoil effect radiolysis. On the other hand, 225Ac-EDTMP was more stable than DOTA-peptide radiolabelled compounds. 225Ac-EDTMP was produced with more than 95% radiochemical yield and 99% radiochemical purity. CONCLUSION: A detailed chemistry study was presented for the synthesis of 225Actinium derivatives in mild conditions with absolute radiochemical purities and high yields. The experimental results showed that 225Ac-EDTMP could be a suitable radiopharmaceutical alternative for bone metastases arising from primer tumors as a cocktail therapy.

Superiority of 68Ga-FAPI PET/CT scan in detecting additional lesions compared to 18FDG PET/CT scan in breast cancer.

PURPOSE: We compared the ability of 68Ga-FAPI PET//CT with 18FDG PET/CT imaging techniques to detect additional lesions in breast cancer patients that may affect further chemotherapy options. METHODS: A total of 48 patients with breast cancer underwent concurrent 68Ga-FAPI-04 and 18FDG PET/CT regardless of whether they had received chemotherapy or not in the last month before imaging. Both modalities were compared according to various parameters: clinical/pathological features, number of lesions detected, activity uptake (SUVmax), and the effect on the evaluation of response to treatment in the post-chemotherapy group. RESULTS: This retrospective study included 48 patients with breast cancer (mean age 53.3 ± 11.7 years; IDC 89.6%; ILC 10.4%). In the comparison of both modalities, no statistical significance was obtained in terms of the pathological characteristics of the patients. More lesions were demonstrated in all categorized regions in 68Ga-FAPI PET/CT imaging with higher uptake values compared to 18FDG PET/CT in this study. In the treatment response evaluation of the post-chemotherapy group, 12 cases (12/24) who were evaluated as PMR, CMR, or SD according to 18FDG PET/CT results were later accepted as PD due to newly detected lesions in complementary 68Ga-FAPI PET/CT imaging and treatment of patients was managed accordingly by clinicians. CONCLUSION: It was determined that 68Ga-FAPI PET/CT was superior to 18FDG PET/CT in terms of accuracy and it was thought that 68Ga-FAPI PET/CT could be utilized as an additional complementary imaging to 18FDG PET/CT. Moreover, 68Ga-FAPI PET/CT, with its significant theranostic potential, could become a key element in predicting the pathological response of breast cancer patients in further researches.

Fully-automated synthesis of 177Lu labelled FAPI derivatives on the module modular lab-Eazy.

BACKGROUND: To the best of our knowledge, manually production of [177Lu]Lu-FAPI radiopharmaceutical derivatives has been only described in literature. In this work, a fully-automated [177Lu]Lu-FAPI synthesis has been well designed for the first time using commercially available synthesis module. In addition to the development of an automated system with disposable cassette, quality control (QC) and stability studies were comprehensively presented. RESULTS: A fully automated synthesis of [177Lu]Lu-FAPI derivatives was achieved on the Modular Lab Eazy (ML Eazy) with high radiochemical yield ([177Lu]Lu-FAPI-04; 88% ± 3, [177Lu]Lu-FAPI-46; 86% ± 3). Chromatographic analysis indicated the formation of radiosynthesis with an absolute radiochemical purity (99%). Stability experiments clarified the durability of the products within 4 days. All obtained specifications are consistent to European Pharmacopoeia. CONCLUSION: A fully automated synthesis of [177Lu]Lu-FAPI radiopharmaceuticals was accomplished regarding quality control standards and quality assurance by using commercially available a modular approach namely ML Eazy with disposable customized cassette and template.

Fluorescent detection of dipicolinic acid as a biomarker of bacterial spores using lanthanide-chelated gold nanoparticles.

Gold nanoparticles (GNPs) functionalized with ethylenediamine-lanthanide complexes (Eu-GNPs and Tb-GNPs) were used for the selective fluorescent detection of dipicolinic acid (DPA), a unique biomarker of bacterial spores, in water. Particles were characterized by transmission electron microscopy and zeta potential measurements. The coordination of DPA to the lanthanides resulted in the enhancement of the fluorescence. A selective response to DPA was observed over the nonselective binding of aromatic ligands. The ligand displacement strategy were also employed for the ratiometric fluorescent detection of DPA. 4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedion (TFNB) was chosen as an antenna to synthesize ternary complexes. The addition of DPA on EuGNP:TFNB ternary complex quenched the initial emission of the complex at 615nm and increased the TFNB emission at 450nm when excited at 350nm. The results demonstrated that the ratiometric fluorescent detection of DPA was achieved by ligand displacement strategy.

Synthesis and Characterization of Nearly Monodisperse Pt Nanoparticles for C1 to C3 Alcohol Oxidation and Dehydrogenation of Dimethylamine-borane (DMAB).

Highly efficient nearly monodisperse Pt NPs catalyze C1 to C3 alcohol oxidation with very high electrochemical activities and provides one of the highest catalytic activities (TOF = 21.50 h(-1)) in the dehydrogenation of DMAB at room temperature. The exceptional stability towards agglomeration, leaching and CO poisoning for the prepared catalyst allow these particles to be recycled and reused in the catalysis of both DMAB dehydrogenation and C1 to C3 alcohol oxidation. After four subsequent reaction and recovery cycles, catalyst retained ≥ 80% activity towards the complete dehydrogenation of DMAB. The prepared catalyst structures were determined by the X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), atomic force microscopy (AFM) and transmission electron microscopy (TEM) respectively.

Multicomponent assembly of macrocycles and polymers by coordination of pyridyl ligands to 1,4-bis(benzodioxaborole)benzene.

Multicomponent reactions between 1,4-benzenediboronic acid, catechol, and different pyridyl ligands are reported. The condensation of 1,4-benzenediboronic acid with catechol gives 1,4-bis(benzodioxaborole)benzene. Upon crystallization, the ester aggregates with the N-donor ligands through dative B-N bonds. Depending on the nature of the pyridyl ligand, molecularly defined macrocycles or polymeric structures are obtained. 1D polymers are formed with 4,4-bipyridine and 1,2-di(4-pyridyl)ethylene, whereas a 2D network is obtained with the tetradentate ligand tetra(4-pyridylphenyl)ethylene. These results highlight the utility of dative B-N bonds in structural supramolecular chemistry and crystal engineering.

Dicarboxylate-bridged ruthenium complexes as building blocks for molecular nanostructures.

Ruthenium complexes with bridging dicarboxylate ligands were combined with 1,2-di-4-pyridylethylene (dpe), 2,4,6-tri-4-pyridyltriazine (4-tpt), or 2,4,6-tri-3-pyridyltriazine (3-tpt) to give a tetranuclear rectangle or hexanuclear coordination cages. The cages display a trigonal-prismatic geometry, as evidenced by single-crystal X-ray crystallography. The 4-tpt-based cages are able to encapsulate polyaromatic molecules such as pyrene, triphenylene, or coronene, whereas the 3-tpt-based cages were found to be incompetent hosts for these guests.

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study.

Oxazolidinones can be synthesized starting from cyclic biscarbamates via a palladium-catalyzed reaction. To test the proposed mechanism of this reaction, first, bicyclonorcarene endoperoxides derived from cyano and carbomethoxy cycloheptatrienes were synthesized and converted into the corresponding diols. The reaction of diols with toluenesulfonyl isocyanate followed by a palladium catalyzed reaction furnished oxazolidinone derivatives in similar yields. It was shown that, if one face of the double bond is blocked by substituents such as H or CN, the reaction also takes place. On the basis of these results, it was assumed that an antiperiplanar orientation of the metal and nucleophile is not necessary to form oxazolidinones. The metal is probably bonded to the allylic system from the same face as the nucleophile.

Endo- and exo-configured cyclopropylidenes incorporated into the norbornadiene skeleton: generation, rearrangement to allenes, and the effect of remote substituents on carbene stability.

For the synthesis of endo-configured cyclopropylidenes annelated to benzonorbornadiene, first the exo-bridge hydrogen in benzonorbornadiene was blocked with ethyl, bromine, and methoxy groups. All efforts to add dichloro-, dibromo-, or fluorobromocarbenes to ethylbenzonorbornadiene failed. However, addition of fluorobromocarbene to bromo- or methoxybenzonorbornadiene gave the corresponding cyclopropane derivatives bearing two halogen atoms, which were submitted to the Doering-Moore-Skattebøl reaction. The formed allene intermediates were trapped with furan. The reactivity of the double bonds in substituted benzonorbornadienes was analyzed by determination of the pyramidalization angles. Furthermore, the relative energies of various carbenes and their rearrangement to allene were studied at B3LYP/6-31G(d) level.