Comparison of Diagnostic Performance of Three-Dimensional Positron Emission Mammography versus Whole Body Positron Emission Tomography in Breast Cancer.

Objective: To compare the diagnostic performance of three-dimensional (3D) positron emission mammography (PEM) versus whole body positron emission tomography (WBPET) for breast cancer. Methods: A total of 410 women with normal breast or benign or highly suspicious malignant tumors were randomized at 1 : 1 ratio to undergo 3D-PEM followed by WBPET or WBPET followed by 3D-PEM. Lumpectomy or mastectomy was performed on eligible participants after the scanning. Results: The sensitivity and specificity of 3D-PEM were 92.8% and 54.5%, respectively. WBPET showed a sensitivity of 95.7% and specificity of 56.8%. After exclusion of the patients with lesions beyond the detecting range of the 3D-PEM instrument, 3D-PEM showed higher sensitivity than WBPET (97.0% versus 95.5%, P = 0.913), particularly for small lesions (<1 cm) (72.0% versus 60.0%, P = 0.685). Conclusions: The 3D-PEM appears more sensitive to small lesions than WBPET but may fail to detect lesions that are beyond the detecting range. This study was approved by the Ethics Committee (E2012052) at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China). The instrument positron emission mammography (PEMi) was approved by China State Food and Drug Administration under the registration number 20153331166.

Synthesis and 18F-labeling of the analogues of Omecamtiv Mecarbil as a potential cardiac myosin imaging agent with PET.

INTRODUCTION: Cardiac myosin is a potential molecular target for heart failure imaging since its changes can be used to assess the function of heart. In this study, two analogues of Omecamtiv Mecarbil, which is the first selective activator of cardiac myosin, were synthesized and radio-labeled with (18)F. Then the radio-compounds were evaluated as potential cardiac myosin imaging agent. METHODS: The labeling precursor and the nonradioactive compounds were synthesized and characterized by IR, (1)H NMR, (13)C NMR and MS analysis. By substituting bromo of precursors with (18)F, the radiolabeled compounds [(18)F]8 and [(18)F]10 were prepared and further evaluated for their in vitro physicochemical properties, stabilities, protein binding assay and ex vivo biodistribution. RESULTS: Starting with [(18)F]F(-) Kryptofix 2.2.2./K2CO3 solution, the total reaction time for [(18)F]8 and [(18)F]10 was about 40 min respectively, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 12.47% ± 3.30% (n=8), the radiochemical purity, 98% or more. Their specific activity was estimated as 50 GBq/µmol. Both [(18)F]8 and [(18)F]10 could be stable after incubation in water at room temperature and in serum or binding buffer at 37 °C for 3h. Biodistribution in normal mice showed that both [(18)F]8 and [(18)F]10 have good heart uptake at 2 min post-injection time. Compound [(18)F]10 has better heart retention and higher heart to background ratios than those of [(18)F]8. In vitro protein binding assay demonstrates that [(18)F]10 may have high affinity with myosin from bovine heart. CONCLUSION: [(18)F]8 and [(18)F]10 were synthesized with good radiochemical yield and high radiochemical purity (>98%). One of the compounds ([(18)F]10) has higher bovine heart myosin binding affinity and better heart/liver ratio. It will be further evaluated as a potent cardiac myosin imaging agent in normal and systolic heart failure model with positron emission tomography in the future.

Fluorine-18 labeled galactosyl-neoglycoalbumin for imaging the hepatic asialoglycoprotein receptor.

UNLABELLED: Asialoglycoprotein receptors (ASGP-R) are well known to exist on the mammalian liver, situate on the surface of hepatocyte membrane. Quantitative imaging of asialoglycoprotein receptors could estimate the function of the liver. (99m)Tc labeled galactosyl-neoglycoalbumin (NGA) and diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) have been developed for SPECT imaging and clinical used in Japan. In this study, we labeled the NGA with (18)F to get a novel PET tracer [(18)F]FNGA and evaluated its hepatic-targeting efficacy and pharmacokinetics. METHODS: NGA was labeled with (18)F by conjugation with N-succinimidyl-4-(18)F-fluorobenzoate ([(18)F]SFB) under a slightly basic condition. The in vivo metabolic stability of [(18)F]FNGA was determined. Ex vivo biodistribution of [(18)F]FNGA and blocking experiment was investigated in normal mice. MicroPET images were acquired in rat with and without block at 5 min and 15 min after injection of the radiotracer (3.7MBq/rat), respectively. RESULTS: Starting with (18)F(-) Kryptofix 2.2.2./K(2)CO(3) solution, the total reaction time for [(18)F]FNGA is about 150 min. Typical decay-corrected radiochemical yield is about 8-10%. After rapid purified with HiTrap desalting column, the radiochemical purity of [(18)F]FNGA was more than 99% determined by radio-HPLC. [(18)F]FNGA was metabolized to produce [(18)F]FB-Lys in urine at 30 min. Ex vivo biodistribution in mice showed that the liver accumulated 79.18+/-7.17% and 13.85+/-3.10% of the injected dose per gram at 5 and 30 min after injection, respectively. In addition, the hepatic uptake of [(18)F]FNGA was blocked by pre-injecting free NGA as blocking agent (18.55+/-2.63%ID/g at 5 min pi), indicating the specific binding to ASGP receptor. MicroPET study obtained quality images of rat at 5 and 15 min post-injection. CONCLUSION: The novel ASGP receptor tracer [(18)F]FNGA was synthesized with high radiochemical yield. The promising biological properties of [(18)F]FNGA afford potential applications for assessment of hepatocyte function in the future. It may provide quantitative information and better resolution which particularly help to the liver surgery.