Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMAB®

Purpose: The chimeric monoclonal antibody (mAb) chDAB4 (APOMAB®) targets the Lupus associated (La)/Sjögren Syndrome-B (SSB) antigen, which is over-expressed in tumors but only becomes available for antibody binding in dead tumor cells. Hence, chDAB4 may be used as a novel theranostic tool to distinguish between responders and nonresponders early after chemotherapy. Here, we aimed to ascertain which positron emitter, Zirconium-89 ([⁸⁹Zr]Zr(IV)) or Iodine-124 ([¹²⁴I]I), was best suited to label chDAB4 for post-chemotherapy PET imaging of tumor-bearing mice and to determine which of two different bifunctional chelators provided optimal tumor imaging by PET using [⁸⁹Zr]Zr(IV)-labeled chDAB4. Methods: C57BL/6 J mice bearing subcutaneous syngeneic tumors of EL4 lymphoma were either untreated or given chemotherapy, then administered radiolabeled chDAB4 after 24 h with its biodistribution examined using PET and organ assay. We compared chDAB4 radiolabeled with [⁸⁹Zr] Zr(IV) or [¹²⁴I] I, or [⁸⁹Zr]Zr-chDAB4 using either DFO-NCS or DFOSq as a chelator. Results: After chemotherapy, [⁸⁹Zr]Zr-chDAB4 showed higher and prolonged mean (± SD) tumor uptake of 29.5 ± 5.9 compared to 7.8 ± 1.2 for [¹²⁴I] I -chDAB4. In contrast, antibody uptake in healthy tissues was not affected. Compared to DFO-NCS, DFOSq did not result in significant differences in tumor uptake of [⁸⁹Zr]Zr-chDAB4 but did alter the tumor:liver ratio in treated mice 3 days after injection in favour of DFOSq (8.0 ± 1.1) compared to DFO-NCS (4.2 ± 0.7). Conclusion: ImmunoPET using chDAB4 radiolabeled with residualizing [⁸⁹Zr] Zr(IV) rather than [¹²⁴I] I optimized post-chemotherapy tumor uptake. Further, PET imaging characteristics were improved by DFOSq rather than DFO-NCS. Therefore, the radionuclide/chelator combination of [⁸⁹Zr] Zr(IV) and DFOSq is preferred for the imminent clinical evaluation of chDAB4 as a selective tumor cell death radioligand.Vasilios Liapis, William Tieu, Stacey E. Rudd, Paul S. Donnelly, Nicole L. Wittwer, Michael P. Brown, and Alexander H. Staudache

Positron emission tomographic imaging of tumor cell death using zirconium-89-labeled APOMAB(R) following cisplatin chemotherapy in lung and ovarian cancer xenograft models

Published online 06 July 2021Purpose Early detection of tumor treatment responses represents an unmet clinical need with no approved noninvasive methods. DAB4, or its chimeric derivative, chDAB4 (APOMAB®) is an antibody that targets the Lupus associated antigen (La/SSB). La/SSB is over-expressed in malignancy and selectively targeted by chDAB4 in cancer cells dying from DNA-damaging treatment. Therefore, chDAB4 is a unique diagnostic tool that detects dead cancer cells and thus could distinguish between treatment responsive and nonresponsive patients. Procedures In clinically relevant tumor models, mice bearing subcutaneous xenografts of human ovarian or lung cancer cell lines or intraperitoneal ovarian cancer xenografts were untreated or given chemotherapy followed 24h later by chDAB4 radiolabeled with [⁸⁹Zr]ZrIV. Tumor responses were monitored using bioluminescence imaging and caliper measurements. [⁸⁹Zr]Zr-chDAB4 uptake in tumor and normal tissues was measured using an Albira SI Positron-Emission Tomography (PET) imager and its biodistribution was measured using a Hidex gamma-counter. Results Tumor uptake of [⁸⁹Zr]Zr-chDAB4 was detected in untreated mice, and uptake significantly increased in both human lung and ovarian tumors after chemotherapy, but not in normal tissues. Conclusion Given that tumors, rather than normal tissues, were targeted after chemotherapy, these results support the clinical development of chDAB4 as a radiodiagnostic imaging agent and as a potential predictive marker of treatment response.Vasilios Liapis, William Tieu, Nicole L. Wittwer, Tessa Gargett, Andreas Evdokiou, Prab Takhar, Stacey E. Rudd, Paul S. Donnelly, Michael P. Brown, Alexander H. Staudache

Status of adsorptive removal of dye from textile industry effluent

Textile industry is the key user of dyes and hence the prime source of water pollution, which risks aquatic as well as human life. There are various physical, chemical, and biological methods for dye removal, but most convincing is adsorption due to its simplicity. The extensive research has been carried out in this field which has brought a wide range of adsorbents in reach of industries. Freshly obtained off beat adsorbents in addition to direct one present have been used. The present paper aims at the broad classification of adsorbents recently introduced to the arena. The division of adsorbents comprises conventional means like activated carbon ( commercial and derived), zeolite, and other nonconventional adsorbents as natural material, wastes, or even especially designed adsorbents, which are inexpensive and clean to use. Also, the investigations done regarding adsorption lately have been compared with respect to their results. The efficacy of each operation is under grave discussion. Up to 95% of the dye removal was observed in many cases with the adsorbent doses in the range of 1-20 g L (1)National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2012-001400]; Korea government (MEST) [2012-0000609]This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012-001400) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2012-0000609)