Synergistic attraction of Western black-legged ticks, Ixodes pacificus, to CO2 and odorant emissions from deer-associated microbes.

Foraging ticks reportedly exploit diverse cues to locate their hosts. Here, we tested the hypothesis that host-seeking Western black-legged ticks, Ixodes pacificus, and black-legged ticks, I. scapularis, respond to microbes dwelling in sebaceous gland secretions of white-tailed deer, Odocoileus virginianus, the ticks' preferred host. Using sterile wet cotton swabs, microbes were collected from the pelage of a sedated deer near forehead, preorbital, tarsal, metatarsal and interdigital glands. Swabs were plated on agar, and isolated microbes were identified by 16S rRNA amplicon sequencing. Of 31 microbial isolates tested in still-air olfactometers, 10 microbes induced positive arrestment responses by ticks, whereas 10 others were deterrent. Of the 10 microbes prompting arrestment by ticks, four microbes-including Bacillus aryabhattai (isolates A4)-also attracted ticks in moving-air Y-tube olfactometers. All four of these microbes emitted carbon dioxide and ammonia as well as volatile blends with overlapping blend constituents. The headspace volatile extract (HVE) of B. aryabhattai (HVE-A4) synergistically enhanced the attraction of I. pacificus to CO2. A synthetic blend of HVE-A4 headspace volatiles in combination with CO2 synergistically attracted more ticks than CO2 alone. Future research should aim to develop a least complex host volatile blend that is attractive to diverse tick taxa.

Determination of distribution coefficients of mercury and gold on selected extraction chromatographic resins - towards an improved separation method of mercury-197 from proton-irradiated gold targets.

Radioisotope mercury-197g (197gHg, half-life: 64.14 h) along with its metastable isomer (197mHg, half-life: 23.8 h) are potential candidates for targeted Meitner-Auger electron therapy due to their suitable decay properties. Their production can be achieved via proton irradiation of a natural gold target, but the number of studies surrounding their separation from an irradiated gold target is limited. This study focuses on the determination of distribution coefficients (Kd) of gold (III) and mercury (II) on seven extraction chromatographic resins. Mercury Kd were measured by means of radiotracers and Inductively Coupled Plasma Mass Spectrometry (ICP_MS); values obtained from the two methods were generally in good agreement. These results can provide insight on Hg and Au chemistry and aid in the design of improved separation system(s).

Radiolabeling of a polypeptide polymer for intratumoral delivery of alpha-particle emitter, 225Ac, and beta-particle emitter, 177Lu.

INTRODUCTION: Radiotherapy of cancer requires both alpha- and beta-particle emitting radionuclides, as these radionuclide types are efficient at destroying different types of tumors. Both classes of radionuclides require a vehicle, such as an antibody or a polymer, to be delivered and retained within the tumor. Polyglutamic acid (pGlu) is a polymer that has proven itself effective as a basis of drug-polymer conjugates in the clinic, while its derivatives have been used for pretargeted tumor imaging in a research setup. trans-Cyclooctene (TCO) modified pGlu is suitable for pretargeted imaging or therapy, as well as for intratumoral radionuclide therapy. In all cases, it becomes indirectly radiolabeled via the bioorthogonal click reaction with the tetrazine (Tz) molecule carrying the radionuclide. In this study, we report the radiolabeling of TCO-modified pGlu with either lutetium-177 (177Lu), a beta-particle emitter, or actinium-225 (225Ac), an alpha-particle emitter, using the click reaction between TCO and Tz. METHODS: A panel of Tz derivatives containing a metal ion binding chelator (DOTA or macropa) connected to the Tz moiety directly or through a polyethylene glycol (PEG) linker was synthesized and tested for their ability to chelate 177Lu and 225Ac, and click to pGlu-TCO. Radiolabeled 177Lu-pGlu and 225Ac-pGlu were isolated by size exclusion chromatography. The retention of 177Lu or 225Ac by the obtained conjugates was investigated in vitro in human serum. RESULTS: All DOTA-modified Tzs efficiently chelated 177Lu resulting in average radiochemical conversions (RCC) of >75%. Isolated radiochemical yields (RCY) for 177Lu-pGlu prepared from 177Lu-Tzs ranged from 31% to 55%. TLC analyses detected <5% unchelated 177Lu for all 177Lu-pGlu preparations over six days in human serum. For 225Ac chelation, optimized RCCs ranged from 61 ± 34% to quantitative for DOTA-Tzs and were quantitative for the macropa-modified Tz (>98%). Isolated radiochemical yields (RCY) for 225Ac-pGlu prepared from 225Ac-Tzs ranged from 28% to 51%. For 3 out of 5 225Ac-pGlu conjugates prepared from DOTA-Tzs, the amount of unchelated 225Ac stayed below 10% over six days in human serum, while 225Ac-pGlu prepared from macropa-Tz showed a steady release of up to 37% 225Ac. CONCLUSION: We labeled TCO-modified pGlu polymers with alpha- and beta-emitting radionuclides in acceptable RCYs. All 177Lu-pGlu preparations and some 225Ac-pGlu preparations showed excellent stability in human plasma. Our work shows the potential of pGlu as a vehicle for alpha- and beta-radiotherapy of tumors and demonstrated the usefulness of Tz ligation for indirect radiolabeling.