Automated light-induced synthesis of 89Zr-radiolabeled antibodies for immuno-positron emission tomography

Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

Automated Light-Induced Synthesis of 89Zr-Radiolabeled Antibodies for Immuno-Positron Emission Tomography

Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography (PET) imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in <25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our Good Laboratory Practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in <25 min with an overall decay-corrected radiochemical yield of 20.1±2.4% (n=3), a radiochemical purity >99%, and chemical purity >99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

Low-Dose Radiation Therapy for COVID-19 Pneumonia: review

The use of low-dose radiation therapy (LDRT) in patients with pneumonia from 1905 to 1943 provided positive results in 83.08 % of cases. Interest in LDRT is supported by researchers of radiation hormesis in the 21st century. Attention is drawn to the dynamics of coronavirus infection in the regions of Ukraine and the Kirovograd region with a minimum incidence. It is known that 95 % of uranium ore deposits in Ukraine are concentrated in the Kirovograd region. The positive experience of LDRT in Iran, India, USA, Spain for the treatment of patients with COVID-19 is described. LDRT (<100 cGy) is known to be anti-inflammatory, and therefore pulmonary LDRT has the potential to reduce the severity of pneumonia and reduce mortality. LDRT deserves a clinical study. A new direction in radiation therapy – Auger therapy based on radiolabeled antibodies – is planned to be used as a molecular targeting radiotherapy agent directly to the SARS-CoV-2.