[en] Oriented polycrystalline CoFe_2O_4 have been prepared via a ceramic method. The CoFe_2O_4 powder was mixed with polyvinyl alcohol solution to produce semisolid slurries. The slurries were oriented under a magnetic field of 2 T, and were then sintered at 1623 K. The maximum magnetostriction λ_s up to −270×10"−"6 and strain derivative (dλ/dH)_m_a_x of 7.7×10"−"9 m/A were achieved for oriented samples. Results show that a preferred <001> orientation has been obtained within oriented sample. - Highlights: • Oriented polycrystalline CoFe_2O_4 had been prepared by a ceramic method firstly. • Textures of oriented samples were characterized using EBSD technology and results shown that a <001> fiber texture had been obtained. • λ_s of −270 ppm was achieved in oriented sample, which is 90% higher in magnitude than that of non-oriented sample. • The maximum strain derivatives (dλ/dH)_m_a_x had been great increased from 2.2×10"−"9 m/A for non-oriented sample to 7.7×10"−"9 m/A for oriented one.

[en] Xeloda (Capecitabine), a prodrug of antitumor agent 5-fluorouracil, is the first and only oral fluoropyrimidine to be approved for use as second-line therapy in metastatic breast cancer, colorectal cancer, and other solid malignancies. Fluorine-18 labeled Xeloda may serve as a novel radiotracer for positron emission tomography (PET) to image enzymes such as thymidine phosphorylase and uridine phosphorylase in cancers. The precursor 2',3'-di-O-acetyl-5'-deoxy-5-nitro-N⁴-(pentyloxycarbonyl)cytidine (11) was synthesized from D-ribose and cytosine in 8 steps with approximately 18% overall chemical yield. The reference standard 5'-deoxy-5-fluoro-N⁴-(pentyloxycarbonyl)cytidine (Xeloda; 1) was synthesized from D-ribose and 5-fluorocytosine in eight steps with approximately 28% overall chemical yield. The target radiotracer 5'-deoxy-5-[¹⁸F]fluoro-N⁴-(pentyloxycarbonyl)cytidine ([¹⁸F]Xeloda; [¹⁸F]1) was prepared by nucleophilic substitution of the nitro-precursor with K¹⁸F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20-30% radiochemical yields

[en] Novel radiolabeled O⁶-benzylguanine (O⁶-BG) derivatives, 2-amino-6-O-[¹¹C]-[(methoxymethyl)benzyloxy]-9-methyl purines ([¹¹C]p-O⁶-AMMP, 1a; [¹¹C]m-O⁶-AMMP, 1b; [¹¹C]o-O⁶-AMMP, 1c), 2-amino-6-O-benzyloxy-9-[¹¹C]-[(methoxycarbonyl)methyl]purine ([¹¹C]ABMMP, 2), and 2-amino-6-O-benzyloxy-9-[¹¹C]-[(4'-methoxycarbonyl)benzyl]purine ([¹¹C]ABMBP, 3), have been synthesized for evaluation as new potential positron emission tomography (PET) imaging agents for the DNA repair protein O⁶-alkylguanine-DNA alkyltransferase (AGT) in breast cancer. The appropriate precursors for radiolabeling were obtained in two to three steps from starting material 2-amino-6-chloropurine with moderate to excellent chemical yields. Tracers were prepared by O-[¹¹C]methylation of hydroxymethyl or acid precursors using [¹¹C]methyl triflate. Pure target compounds were isolated by solid-phase extraction (SPE) purification procedure in 45-65% radiochemical yields (decay corrected to end of bombardment), and a synthesis time of 20-25 min. The activity of unlabeled standard samples of 1-3 was evaluated via an in vitro AGT oligonucleotide assay. Preliminary findings from biological assay indicate the synthesized analogs have similar strong inhibitory effectiveness on AGT in comparison with the parent compound O⁶-BG. The results warrant further evaluation of these radiotracers as new potential PET imaging agents for the DNA repair protein AGT in breast cancer in vivo

[en] A series of ¹¹C-labeled analogs of the acetylcholinesterase (AChE) inhibitor pyridostigmine have been synthesized for evaluation as new potential positron emission tomography (PET) imaging agents for heart AChE. The appropriate precursors for radiolabeling were slightly modified from commercial reagents. The new tracers [¹¹C]pyridostigmine (1), [¹¹C]para-pyridostigmine (2) and [¹¹C]ortho-pyridostigmine (3) were prepared by N-[¹¹C]methylation of the precursors using [¹¹C]methyl triflate. Pure target compounds were isolated by a solid-phase extraction (SPE) purification procedure with 60-85% radiochemical yields (decay corrected to end of bombardment), and a synthesis time of 10-15 min. The initial PET dynamic studies of compounds (1-3) in rat heart showed rapid heart uptake and blood pool clearance to give high quality heart images. These results suggest the new tracers delineate the heart very clearly and could be potential heart AChE imaging agents

[en] [¹¹C]Choline has been evaluated as a potential positron emission tomography (PET) marker for imaging of breast cancer. The biodistribution of [¹¹C]choline was determined at 45 min post iv injection in MCF-7's transfected with IL-1alpha implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptake of [¹¹C]choline in these tumors was high, 2.0% dose/g in MCF-7's transfected with IL-1alpha implanted mice and 1.8% dose/g in MDA-MB-435 implanted mice; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.7 (T/M, MCF-7's), 2.1 (T/M, MDA-MB-435) and 6.9 (T/B, MCF-7's), 12.5 (T/B, MDA-MB-435), respectively; the tumor/muscle ratios are moderate, and the tumor/blood ratios are high. The micro-PET imaging of [¹¹C]choline in both breast cancer athymic mice was acquired for 15 min from a MCF-7's transfected with IL-1alpha and/or MDA-MB-435 implanted mouse at 45 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, Indy-PET II scanner, developed in our laboratory, which showed the uptake of [¹¹C]choline in MCF-7's transfected with IL-1alpha tumor or MDA-MB-435 tumor implanted in a nude athymic mouse. These results suggest that [¹¹C]choline may be a potential PET breast cancer imaging agent

[en] (S)-2-(4'-[¹¹C]methoxybiphenyl-4-sulfonylamino)-3-methylbutyric acid ([¹¹C]MSMA) and N-hydroxy-(R)-2-[[(4'-[¹¹C]methoxyphenyl)sulfonyl]benzylamino]-3- methylbutanamide ([¹¹C]CGS 25966), carbon-11 labeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) cancer biomarkers. [¹¹C]MSMA was prepared by appropriate precursory droxybiphenyl-4-sulfonylamino)-3-methylbutyric acid tert-butyl ester, which was synthesized in eight steps from amino acid (L)-valine in 39.4% chemical yield. This precursor was labeled by [¹¹C]methyl triflate through O-[¹¹C]methylation method at the hydroxyl position of biphenol under basic conditions, followed by a quick acid hydrolysis and isolated by solid-phase extraction (SPE) purification to produce pure target compound [¹¹C]MSMA in 35-55% radiochemical yield, based on ¹¹CO₂, decay corrected to end of bombardment (EOB), and 20-25 min synthesis time. [¹¹C]CGS 25966 was prepared in our previous work starting from amino acid (D)-valine. The biodistribution of [¹¹C]MSMA and [¹¹C]CGS 25966 were determined at 45 min post iv injection in breast cancer animal models MCF-7's transfected with IL-1α implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptakes of [¹¹C]MSMA and [¹¹C]CGS 25966 in these tumors were 0.95 and 0.42%dose/g in MCF-7's transfected with IL-1α implanted mice, 0.98 and 1.53%dose/g in MDA-MB-435 implanted mice, respectively; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.21 and 1.09 (T/M, MCF-7's), 0.99 and 0.84 (T/B, MCF-7's), 1.38 and 1.27 (T/M, MDA-MB-435), 1.27 and 1.95 (T/B, MDA-MB-435), respectively. The micro-PET images of [¹¹C]MSMA and [¹¹C]CGS 25966 in both breast cancer athymic mice were acquired for 15 min from a MCF-7's transfected with IL-1α and/or MDA-MB-435 implanted mouse at 45 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, Indy-PET II scanner, developed in our laboratory, which showed both tumors were invisible with both tracers. The results were compared. From our results, we concluded that both [¹¹C]MSMA and [¹¹C]CGS 25966 might be unsuitable as PET tracers for cancer imaging

[en] A series of [¹¹C]methyl-halo-CGS 27023A analogs (2-F, 1a; 4-F, 1b; 2-Cl, 1c; 3-Cl, 1d; 4-Cl, 1e; 2-Br, 1f; 3-Br, 1g; 4-Br, 1h; 4-I, 1i), novel radiolabeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) breast cancer imaging agents. The precursors halo-CGS 27023A analogs (2-F, 6a; 4-F, 6b; 2-Cl, 6c; 3-Cl, 6d; 4-Cl, 6e; 2-Br, 6f; 3-Br, 6g; 4-Br, 6h; 4-I, 6i) for radiolabeling were obtained in four steps from starting material amino acid D-valine with moderate to excellent chemical yields. Precursors were labeled by [¹¹C]methyl triflate through ¹¹C-O-methylation method at the aminohydroxyl position under basic conditions and isolated by solid-phase extraction (SPE) purification to produce pure target compounds in 40-60% radiochemical yields (decay corrected to end of bombardment), in 20-25 min synthesis time

[en] Highlights: • Highly 0 0 1 textured CoFe2O4 had been prepared by magnetic field aligning method. • λ_S of −500 ppm at 1000 Oe and (dλ/dH)_max of −0.97 ppm/Oe at 250 Oe had been obtained. • Anisotropic CoFe2O4 shew great application prospects in sonar detector and sensor. We report the magnetostriction and 0 0 1 texture of anisotropic polycrystalline CoFe2O4. Slurries with well dispersion and low sintering shrinkage are aligned by the magnetic field of 2 T and sintered to prepare highly 0 0 1 textured CoFe2O4 samples. For the anisotropic sample, benefiting from the 0 0 1 fiber texture, a higher magnetostrictive property is achieved than that of isotropic polycrystalline sample prepared by dry compaction. The maximum magnetostriction up to −500 ppm at 1000 Oe is obtained, which reaches 85% of the highest value in single crystal (λ₁₀₀ = −590 ppm). Meanwhile, the maximum strain-field derivative is also improved to −0.97 ppm/Oe at 250 Oe, which is highly beneficial for sonar detector and force sensor applications.

[en] In cervical cancer patients with intermediate-risk factors, the optimal adjuvant therapy is still controversial. We undertook a randomized trial (ClinicalTrials.gov Identifier: NCT01418859) to compare the efficacy and toxicity of concurrent chemoradiotherapy with topotecan and cisplatin with radiotherapy alone in intermediate-risk cervical cancer patients. Eligible patients were randomly assigned to one of three treatment arms including arm A (radiotherapy only,RT), arm B(concurrent chemoradiotherapy only, CCRT), and arm C (concurrent chemoradiotherapy with following consolidation chemotherapy, CCRT + CT). All eligible patients completed external RT (IMRT or 3D-CRT), receiving 45-50Gy /25f uniformly to the pelvis. Concurrent chemotherapy regimen was topotecan 0.75 mg/m² for days 1, 2 and 3, followed by cisplatin 25 mg/m² for days 1, 2 and 3. Three cycles of consolidation chemotherapy regimen was topotecan 1.5 mg/m² for days 1 and 2, and 0.75 mg/m² for day 3; followed by cisplatin 25 mg/m² for days 1, 2 and 3, repeated every 21 days. Adverse events of each group were investigated and compared. Thirty-nine patients enrolled onto the remaining regimens: 14 to RT, 15 to CCRT and 10 to CCRT + CT. Six patients (15.4%) did not complete the protocol treatment. Hematologic toxicity was more frequent and more severe in the CCRT and CCRT + CT arms compared with the RT arm. The incidence of grade 3-4 neutropenia was significantly different statistically between the RT, CCRT and CCRT + RT groups (15.4%, 46.7% and 100%, respectively; P = 0.002). Specially, three patients in CCRT + CT arm of all six patients who did not complete the protocol treatment discontinued planned therapy because of persistent grade 4 neutropenia. However, there were no significant differences in grade 3-4 non-hematologic toxicities between the three groups(all P > 0.05). Recurrence-free survival and overall survival of each group were not analyzed on account of a median follow-up of only 16 months. Concurrent chemoradiotherapy with topotecan and cisplatin showed severe hematologic toxicity in intermediate-risk cervical cancer patients after radical hysterectomy. Thus, the study was closed ahead of schedule. ClinicalTrials.gov Identifier: https://www.clinicaltrials.gov/ct2/show/NCT01418859?term

[en] (2R)-2-[[4-(6-fluorohex-1-ynyl)phenyl]sulfonylamino]-3-methylbutyric acid [¹¹C]methyl ester ([¹¹C]FMAME), a novel carbon-11 labeled matrix metalloproteinase (MMP) inhibitor, has been synthesized for evaluation as new potential positron emission tomography (PET) cancer biomarker. [¹¹C]FMAME was prepared by appropriate precursor (2R)-2-[[4-(6-fluorohex-1-ynyl)phenyl]sulfonylamino]-3-methylbutyric acid (FMA), which was synthesized in six steps from (D)-valine in 71% chemical yield. This acid precursor was labeled by [¹¹C]methyl triflate through O-[¹¹C]methylation method under basic conditions and isolated by solid-phase extraction (SPE) purification to produce pure target compound in 40-55% radiochemical yield, based on ¹¹CO₂, decay corrected to end of bombardment, and 15-20 min synthesis time. The biodistribution of [¹¹C]FMAME was determined at 30 min post IV injection in breast cancer animal models MCF-7 transfected with IL-1α implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptakes of [¹¹C]FMAME in these tumors were 1.13% dose/g in MCF-7 transfected with IL-1α implanted mice and 1.37% dose/g in MDA-MB-435 implanted mice, respectively; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.05 ± 0.29 (T/M, MCF-7's), 0.77 ± 0.20 (T/B, MCF-7's) and 0.99 ± 0.35 (T/M, MDA-MB-435), 1.44 ± 0.69 (T/B, MDA-MB-435), respectively. Pretreatment of MCF-7 transfected with IL-1α tumor-bearing mice with MMP inhibitor FMA had no effect on [¹¹C]FMAME biodistribution. Likewise, pretreatment of MDA-MB-435 tumor-bearing mice with FMA also showed no effect on [¹¹C]FMAME biodistribution. The micro-PET images were acquired for 15 min from a MCF-7 transfected with IL-1α tumor-bearing mouse or a MDA-MB-435 tumor-bearing mouse at 30 min post IV injection of 1 mCi of [¹¹C]FMAME using a dedicated high resolution (<3 mm full-width at half-maximum) PET imaging system (Indy-PET II scanner). The initial dynamic micro-PET images of [¹¹C]FMAME in a MCF-7 transfected with IL-1α tumor-bearing mouse during different time periods of 0-15, 15-30, 30-45 and 45-60 min were performed by Indy-PET II. The PET images clearly showed both tumors were visible with [¹¹C]FMAME. These results suggest that the localization of [¹¹C]FMAME in the tumor is mediated by non-specific processes, and the visualization of [¹¹C]FMAME on the tumor using the Indy-PET II scanner is related to non-specific binding