Imaging Androgen Receptors in Breast Cancer with (18)F-fluoro-5α-dihydrotestosterone-PET: A Pilot Study

Most breast cancers express androgen receptors (AR). This prospective imaging sub-study explored imaging AR with (18)F-fluoro-5α-dihydrotestosterone (FDHT)-PET in patients with metastatic breast cancer (MBC) receiving selective AR modulation (SARM) therapy (GTx-024, GTx, Inc). Methods: 11 post-menopausal women with estrogen receptor positive MBC underwent FDHT-PET/CT at baseline, 6, and 12 weeks after starting SARM therapy. Abnormal tumor FDHT uptake was quantified using maximum SUV (SUVmax). AR status was determined from tumor biopsy specimens. FDHT-SUVmax percent change between scans was calculated. Best overall response was categorized as clinical benefit (CB: non-progressive disease [PD]), or PD using RECIST 1.1. Results: Median baseline FDHT-SUVmax was 4.1 (range 1.4-5.9) for AR+ tumors versus 2.3 (range 1.5-3.2) for AR- tumors (p=0.22). Quantitative AR expression and baseline FDHT uptake were weakly correlated (Pearson rho=0.39, p=0.30). Seven participants with CB at 12 weeks tended to have larger declines in FDHT uptake compared to those with PD at both 6 (median decline, range: -26.8%, -42.9 to -14.1% vs. -3.7%, -31% to +29%, respectively, p=0.11) and 12 weeks (median decline, range: -35.7%, -69.5 to -7.7% vs. -20.1%, -26.6% to +56.5%, respectively, p=0.17) after starting GTx-024. Conclusion: This hypothesis-generating data suggests that FDHT-PET/CT is worth further study as an imaging biomarker for evaluating response of MBC to SARM therapy and reiterates the feasibility of including molecular imaging in multidisciplinary therapeutic trials

<span style="font-size:12.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-ansi-language: EN-IN;mso-fareast-language:EN-IN;mso-bidi-language:AR-SA" lang="EN-IN">Oxidation of olefins and hydrazones by anodically in <i>situ </i>generated manganese <span style="mso-bidi-font-weight:bold">(III)<b> </b>acetate</span></span>

548-552<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-in;mso-fareast-language:en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">The oxidation of olefins and hydrazones of carbonyl compounds has been performed by using in situ anodically generated milder oxidant Mn(III) acetate at Pt electrode in acetic acid. The oxidation of acyclic olefins leads to the formation of 1,2-diacetate while in the case of cyclic olefin it results in the formation of -lactone ring onto double bond. Further, intermolecular carbolactonization of olefins has been achieved using more reactive carboxylic acid substrate i.e. ethyl hydrogen malonate at room temperature under the similar reaction conditions. Mn(III) acetate oxidation of hydrazones of carbonyl compounds leads to its fragmentation products.</span

<span style="font-size:12.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language:HI" lang="EN-IN">Synthesis and characterization of poly (<i>ortho</i>-anisidine) using quinolinium fluorochromate (QFC) [C₉H₇NH(CrO₃F)] as an oxidizing agent</span>

288-293<span style="font-size:12.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:hi"="" lang="EN-IN">Poly(o-anisidine) has been prepared using quinolinium fluorochromate C9H7NH[CrO3F] (QFC) as an oxidizing agent and the polymer was obtained in good yield. The detailed electrochemical studies have been performed in the presence of QFC in aqueous and non-aqueous media. TG analysis exhibited that the synthesized polymers have relatively high thermal stability. Conductivity of the polymers was found in the range of 10-9 to 10-3 Scm-1 and the magnetic susceptibility measurement show the paramagnetic behaviour. The study also include the structural elucidation and external morphological properties of the synthesized polymers.</span

Prospected epigenetic moderators from natural sources and drug of class NSAIDS as effective treatment options to Prostate cancer

Prostate cancer (PC) is one of the most common and leading cancer amongst the males all around the world. Depending upon it long latency and cost involved in its management and treatment, there is extensive need for more personalized and economical therapeutic approach for its effective therapy. The current review here discusses agents from natural dietary sources and drug class Non-Steroidal Antinflammatory (NSAIDS) that bears chemopreventive potential to regulate PC progression & tumour development and therefore could be devised into effective future treatment strategy against PC along with its metastatic castration-resistant form. Based on the literature search the therapeutic scope of selected agents are delineated, sighting their previous activity and prospects as epigenetic moderators in specific to particular PC causing biomarkers like over expression of AKR1C3, lost intracellular glutathione/glutathione-s-tranferases(GSH/GST) expression, DNA hypermethylation, aberrant cell proliferation and other related factors that are thought to potentiate and aggravate the onset of PC like smoking and use of other narcotics products

Report on the PET/CT Image-Based Radiation Dosimetry of [(18)F]FDHT in Women, a Validated Imaging Agent with New Applications for Evaluation of Androgen Receptor Status in Women with Metastatic Breast Cancer

In a prospective clinical trial, [(18)F]fluoro-5α-dihydrotestosterone ([(18)F]FDHT), the radiolabeled analog of the androgen dihydrotestosterone, was used as a PET/CT imaging agent for in vivo assessment of metastatic androgen receptor-positive breast cancer in postmenopausal women. To our knowledge, this article presents the first report of PET/CT image-based radiation dosimetry of [(18)F]FDHT in women. Methods: [(18)F]FDHT PET/CT imaging was performed on a cohort of 11 women at baseline before the start of therapy and at 2 additional time points during selective androgen receptor modulator (SARM) therapy for androgen receptor-positive breast cancer. Volumes of interest (VOIs) were placed over the whole body and within source organs seen on the PET/CT images, and the time-integrated activity coefficients of [(18)F]FDHT were derived. The time-integrated activity coefficients for the urinary bladder were calculated using the dynamic urinary bladder model in OLINDA/EXM software, with biologic half-life for urinary excretion derived from VOI measurements of the whole body in postvoid PET/CT images. The time-integrated activity coefficients for all other organs were calculated from VOI measurements in the organs and the physical half-life of (18)F. Organ dose and effective dose calculations were then performed using MIRDcalc, version 1.1. Results: At baseline before SARM therapy, the effective dose for [(18)F]FDHT in women was calculated as 0.020 ± 0.0005 mSv/MBq, and the urinary bladder was the organ at risk, with an average absorbed dose of 0.074 ± 0.011 mGy/MBq. Statistically significant decreases in liver SUV or uptake of [(18)F]FDHT were found at the 2 additional time points on SARM therapy (linear mixed model, P \u3c 0.05). Likewise, absorbed dose to the liver also decreased by a small but statistically significant amount at the 2 additional time points (linear mixed model, P \u3c 0.05). Neighboring abdominal organs of the gallbladder wall, stomach, pancreas, and adrenals also showed statistically significant decreases in absorbed dose (linear mixed model, P \u3c 0.05). The urinary bladder wall remained the organ at risk at all time points. Absorbed dose to the urinary bladder wall did not show statistically significant changes from baseline at any of the time points (linear mixed model, P ≥ 0.05). Effective dose also did not show statistically significant changes from baseline (linear mixed model, P ≥ 0.05). Conclusion: Effective dose for [(18)F]FDHT in women before SARM therapy was calculated as 0.020 ± 0.0005 mSv/MBq. The urinary bladder wall was the organ at risk, with an absorbed dose of 0.074 ± 0.011 mGy/MBq

Long-Term Sex- and Genotype-Specific Effects of 56Fe Irradiation on Wild-Type and APPswe/PS1dE9 Transgenic Mice

Space radiation presents a substantial threat to travel beyond Earth. Relatively low doses of high-energy particle radiation cause physiological and behavioral impairments in rodents and may pose risks to human spaceflight. There is evidence that 56Fe irradiation, a significant component of space radiation, may be more harmful to males than to females and worsen Alzheimer&rsquo;s disease pathology in genetically vulnerable models. Yet, research on the long-term, sex- and genotype-specific effects of 56Fe irradiation is lacking. Here, we irradiated 4-month-old male and female, wild-type and Alzheimer&rsquo;s-like APP/PS1 mice with 0, 0.10, or 0.50 Gy of 56Fe ions (1GeV/u). Mice underwent microPET scans before and 7.5 months after irradiation, a battery of behavioral tests at 11 months of age and were sacrificed for pathological and biochemical analyses at 12 months of age. 56Fe irradiation worsened amyloid-beta (A&beta;) pathology, gliosis, neuroinflammation and spatial memory, but improved motor coordination, in male transgenic mice and worsened fear memory in wild-type males. Although sham-irradiated female APP/PS1 mice had more cerebral A&beta; and gliosis than sham-irradiated male transgenics, female mice of both genotypes were relatively spared from radiation effects 8 months later. These results provide evidence for sex-specific, long-term CNS effects of space radiation