Development of an automated production process of [64Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications

Cyclotron-produced copper-64 radioisotope tracers offer the possibility to perform both diagnostic investigation by positron emission tomography (PET) and radiotherapy by a theranostic approach with bifunctional chelators. The versatile chemical properties of copper add to the importance of this isotope in medicinal investigation. [⁶⁴Cu][Cu (ATSM)] has shown to be a viable candidate for imaging of tumor hypoxia; a critical tumor microenvironment characteristic that typically signifies tumor progression and resistance to chemo-radiotherapy. Various production and radiosynthesis methods of [⁶⁴Cu][Cu (ATSM)] exist in labs, but usually involved non-standardized equipment with varying production qualities and may not be easily implemented in wider hospital settings. [⁶⁴Cu][Cu (ATSM)] was synthesized on a modified GE TRACERlab FXN automated synthesis module. End-of-synthesis (EOS) molar activity of [⁶⁴Cu][Cu (ATSM)] was 2.2–5.5 Ci/μmol (HPLC), 2.2–2.6 Ci/μmol (ATSM-titration), and 3.0–4.4 Ci/μmol (ICP-MS). Radiochemical purity was determined to be >99% based on radio-HPLC. The final product maintained radiochemical purity after 20 h. We demonstrated a simple and feasible process development and quality control protocols for automated cyclotron production and synthesis of [⁶⁴Cu][Cu (ATSM)] based on commercially distributed standardized synthesis modules suitable for PET imaging and theranostic studies.     

Methodological Quality Assessment of Meta-analyses and Systematic Reviews of the Relationship Between Periodontal and Systemic Diseases

ObjectivesThe aims of this article are to identify all the published systematic reviews (SRs) and meta-analyses (MAs) that studied the relationship between periodontal and systemic diseases and to assess their quality using 2 scales (the Overview Quality Assessment Questionnaire [OQAQ] and A Measurement Tool to Assess Systematic Reviews [AMSTAR] checklist).MethodsFor SRs and MAs to be included, they should have investigated one of the following systemic diseases: pulmonary conditions, cardiac conditions, endocrine conditions, cancer, blood disorders, psychological conditions, anxiety, depression, mood disorders, and several other diseases. Two investigators screened MEDLINE via PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews. The tools used to evaluate quality were the AMSTAR scale and OQAQ. The protocol was prospectively registered in PROSPERO (CRD42018102208).ResultsThe search strategy found 691 unique articles, 42 of which met the eligibility criteria and were included in this review. Diabetes mellitus was the most investigated disease (14 out of 42 studies), followed by obesity (11 studies) and cardiovascular diseases (5 studies). A total of 40 reviews reported on the characteristics of included studies, and, as per the AMSTAR scale, 39 reviews had an a priori design. The number of reviews that fulfilled the status of publication criterion was the lowest (7 reviews only), followed by the number used in the assessment of publication bias (11 reviews). The number of high-quality reviews was higher with the OQAQ than with the AMSTAR checklist (33 vs 25 studies), but the AMSTAR showed a higher number of medium-quality reviews than the OQAQ (14 vs 6 studies). Both showed the same number of low-quality reviews.ConclusionsHigh-quality SRs and MAs are crucial to understanding the relationship between systemic and periodontal diseases. Medical practitioners must be able to inform patients about oral health and specific periodontal health concerns.     

Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.     

Synthesis of TPH-13, a new tridecapeptide from Phyllomedusa rohdei

The synthesis of TPH-13 (Glp-Glu-Lys-Pro-Tyr-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met-OH), a tridecapeptide isolated from the skin of the South American frog Phyllomedusa rohdei, is described and alternative approaches are discussed.     

bFGF对人毛囊黑素细胞增殖、活化和黑素合成作用的研究

目的　研究碱性成纤维细胞生长因子 (bFGF)对人毛囊黑素细胞 (Hairfolloclemelanocyte ,HFM )增殖活化和黑素合成的影响。方法　体外培养正常人HFM ,观察不同浓度bFGF(0 3～ 1 2ng ml)对HFM形态、增殖、酪氨酸酶活性和黑素含量的影响。结果　bFGF处理HFM 7d后 ,HFM树突增多延长 ,酪氨酸酶活性和黑素含量增加显著高于对照组 (P <0 0 1) ,以 0 6ng ml组为著。结论　bFGF能诱导HFM增殖、酪氨酸酶活性和黑素合成增加     

紫外线照射后哺乳动物细胞DNA的期外合成

本实验用~3H-TdR掺入,液体闪烁测量法测定细胞DNA期外合成的方法,测定了小鼠和大鼠的肠淋巴结细胞、人和大鼠外周血淋巴细胞、S-180V肿瘤细胞等经紫外线照射后的UDS,观察到UDS掺入量随辐照度增加而增加。在同一辐照剂量下,以小鼠肠淋巴结细胞的UDS值最高,其次是人外周血淋巴细胞和S-180V肿瘤细胞,而大鼠外周血淋巴细胞和肠淋巴结细胞最低。     

Synthesis and Properties of Haptens for the Development of Radioimmunoassays for Thioridazine,Mesoridazine, and Sulforidazine

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.