Potential Utility of Radiopharmaceuticals in the Battle Against SARS-Cov-2 and COVID-19 Pandemic

: Coronavirus disease 2019 (COVID-19) pandemic, which has emerged in December 2019 in the city of Wuhan, China, has significantly affected healthcare systems and economies within a short timeframe. Treatment strategies offer alleviation of symptoms in the absence of commercially available specific antiviral agents. Within this context, the introduction of innovative therapeutic approaches against the SARS-CoV-2 virus is a critical need that should be addressed urgently. The anti-inflammatory effect of low dose irradiation has been proposed as a potential therapeutic strategy for COVID-19 pneumonia. Consideration of external beam irradiation for management of COVID-19 pneumonia has prompted the investigation of alternative methods of irradiation with potentially improved toxicity profiles. Theoretically, targeted radiotherapy may have several advantages over conventional external beam radiotherapy owing to the capability to deliver effective radiation doses without adverse irradiation effects. Since radionuclides are conjugated to targeting vectors, such as antibodies and cell surface receptor binding peptides, irradiation may be focused on targeted cells with optimal sparing of surrounding normal tissues. In the context of COVID-19 management, targeted irradiation is expected to compromise SARS-CoV-2 extracellular virions. Targeted radiotherapy may offer a viable means of combating against SARS-CoV-2 virus. There is room for improvement with the need for efficacy, feasibility, and toxicity studies. Although targeted radiotherapy itself may not achieve absolute eradication of virus or virus-infected cells, it may at least serve as a supplementary therapeutic strategy that could be utilized in combination with other antiviral treatments. Further investigations focusing on nuclear medicine, radiopharmaceuticals, and targeted radiotherapy strategies may pave the way for the development of efficacious antiviral treatments which may be utilized in the battle against the current COVID-19 pandemic.

Radiosynthesis and Evaluation of Talazoparib and its Derivatives as PARP-1-Targeting Agents

Poly (ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme in the DNA repair process and the target of several FDA-approved inhibitors. Several of these inhibitors have been radiolabeled for non-invasive imaging of PARP-1 expression or targeted radiotherapy of PARP-1 expressing tumors. In particular, derivatives of olaparib and rucaparib, which have reduced trapping potency by PARP-1 compared to talazoparib, have been radiolabeled for these purposes. Here, we report the first radiosynthesis of [18F]talazoparib and its in vitro and in vivo evaluation. Talazoparib (3a”) and its bromo- or iodo-derivatives were synthesized as racemic mixtures (3a, 3b and 3c), and these compounds exhibit high affinity to PARP-1 (Ki for talazoparib (3a”): 0.65 ± 0.07 nM; 3a: 2.37 ± 0.56 nM; 3b: 1.92 ± 0.41 nM; 3c: 1.73 ± 0.43 nM; known PARP-1 inhibitor Olaparib: 1.87 ± 0.10 nM; non-PARP-1 compound Raclopride: >20,000 nM) in a competitive binding assay using a tritium-labeled PARP-1 radioligand [3H]WC-DZ for screening. [18F]Talazoparib (3a”) was radiosynthesized via a multiple-step procedure with good radiochemical and chiral purities (98%) and high molar activity (28 GBq/μmol). The preliminary biodistribution studies in the murine PC-3 tumor model showed that [18F]talazoparib had a good level of tumor uptake that persisted for over 8 h (3.78 ± 0.55 %ID/gram at 4 h and 4.52 ± 0.32 %ID/gram at 8 h). These studies show the potential for the bromo- and iodo- derivatives for PARP-1 targeted radiotherapy studies using therapeutic radionuclides.

Utilization of nanotechnology in targeted radionuclide cancer therapy: monotherapy, combined therapy and radiosensitization

The rapid progress of nanomedicine field has a great influence on the different tumor therapeutic trends. It achieves a potential targeting of the therapeutic agent to the tumor site with neglectable exposure of the normal tissue. In nuclear medicine, nanocarriers have been employed for targeted delivery of therapeutic radioisotopes to the malignant tissues. This systemic radiotherapy is employed to overcome the external radiation therapy drawbacks. This review overviews studies concerned with investigation of different nanoparticles as promising carriers for targeted radiotherapy. It discusses the employment of different nanovehicles for achievement of the synergistic effect of targeted radiotherapy with other tumor therapeutic modalities such as hyperthermia and photodynamic therapy. Radiosensitization utilizing different nanosensitizer loaded nanoparticles has also been discussed briefly as one of the nanomedicine approach in radiotherapy.