The effect of COVID-19 on nuclear medicine and radiopharmacy activities: A global survey

Globally, COVID-19 affected radiopharmaceutical laboratories. This study sought to determine the economic, service, and research impacts of COVID-19 on radiopharmacy. This online survey was conducted with the participation of employees from nuclear medicine and radiopharmaceutical companies. The socioeconomic status of the individuals was collected. The study was participated by 145 medical professionals from 25 different countries. From this work, it is evident that 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG), and 99mTc-labeled macro aggregated albumin 99mTc-MAA were necessary radiopharmaceuticals used by 57% (83/145and 34% (49/145;) respondents, respectively for determining how COVID infections affect a patient’s body. The normal scheduling procedure for the radiopharmacy laboratory was reduced by more than half (65%; 94/145). In COVID-19, 70% (102/145) of respondents followed the regulations established by the local departments. Throughout the pandemic, there was a 97% (141/145) decrease in all staffing recruitment efforts. The field of nuclear medicine research, as well as the radiopharmaceutical industry, were both adversely affected by COVID-19.

Data collection. The semi-structured questionnaire was divided into two parts: the first, which consisted of five questions, asked for demographic information, and the second, which inquired about respondents' levels of knowledge, attitude, activities, and practises regarding radiopharmacy during a pandemic. The questionnaire was made up entirely of closed-ended questions that required a response in the form of one or more checkboxes to indicate the desired level of response. The questionnaire was designed in such a way that each individual participant had seen the same set of questions in the same order. Each question was intended to be succinct and to the point. To increase the dependability of the responses, they were all recorded using the identical method. Each questionnaire form was subjected to a series of repeated checks to determine its content's reliability. The link to Google Forms and Microsoft Teams was posted, distributed, and circulated via a variety of social media platforms.
Statistical analysis. We used descriptive statistics to characterise the population, their purchase preferences, and their scheduling activities. The paired sample t test was used to determine the reduction in the purchase of materials and radiopharmaceuticals in comparison to normal purchase status before the COVID-19 pandemic. A p-value of 0.05 was statistically significant.
The radiopharmacy activities and the measurements. Purchase and preparation. Radiopharmaceutical preparation was prepared with more care than before pandemic; 75% (108/145) of participants prepared radiopharmaceuticals with greater care than they did before the pandemic (Fig. 3A). The purchase of materials and radiopharmaceuticals were significantly reduced (p < 0.001), in comparison to the normal purchase orders. Purchase was reduced to more than half the normal situation before the pandemic (64%; 64/145). According to 25% respondents, purchase was not affected and remained same as it was before pandemic; however, 5% and 6% reported that processing of some purchase orders was halted and/or put on hold respectively (Fig. 3B).
Scheduling. The procedure for scheduling work in the radiopharmacy lab was decided to be simplified. As a result, 45% (65/145) of all respondents have simplified their appointment scheduling procedures. However, 40% (58/145) respondents claimed that scheduling procedures remained unchanged since the pandemic, while 15% (21/145) claimed that the use of certain radiopharmaceuticals was no longer permitted.

Discussion
According to the findings, the vast majority of respondents worked in the radiopharmacy of the Nuclear Medicine Department. Technologists, who are considered members of the medical profession, comprised the majority of respondents to this survey. Technologists were present and actively involved in providing services to the nuclear medicine department and radiopharmacy operations. Most of the respondents had an experience of more than 6 years in nuclear medicine and radiopharmacy activities. The pandemic has already affected the process of preparing radiopharmaceuticals, so all nuclear departments have instructed their radiopharmacy lab employees to take additional precautions when preparing radiopharmaceuticals. The results showed the interesting observation that 2-[ 18 F]FDG was reported to have been more widely used than normal during the pandemic. COVID-19 exemplifies a well-known principle underlying the use of 2-[ 18 F] FDG in oncology and during inflammatory processes, such as infections. A high uptake on an image is correlated with a high number of viable cancerous or inflammatory cells, an increased glucose metabolism, high levels of GLUT transporter expression, and the activity levels of various glycolytic enzymes or metabolic activity.
People exposed to the SARS-CoV-2 developed respiratory complications, a healthy respiratory system is required for healthy life and to investigate the COVID-19-related complications, the respiratory 99m Tc-MAA represented the second order of radiopharmaceuticals widely used during COVID-19. One of the most important diagnostic procedures that nuclear medicine can perform is an imaging test that uses 99m Tc-MAA radiopharmaceutical. Findings of several studies supported the observation that the frequency of this usage increased during pandemic 20,21 .
The myocardial and bone systems radiopharmaceuticals were performed almost equally during the pandemic due to the importance to exclude the causes of myocardial or skeletal. According to our results and other studies' findings, more than 28% of COVID-19-infected patients exhibit signs of cardiac injury. This is associated with a poor prognosis, a sore throat, a newly developed loss of taste or smell, fever, chills, bone and muscle pain, and other symptoms [22][23][24] .
Although radiopharmacy has many factors, including location, funding, financial and technical factors, and departmental conditions, 2-[ 18 F]FDG and 99m Tc-MAA radiopharmaceuticals were the most prominent used during COVID-19.
The extraordinary presence of radiopharmaceuticals such as 2-[ 18 F]FDG and 99m Tc-MAA at COVID-19 was unaffected by geographical location, radiopharmaceutical production sources, or radiopharmaceutical production types. There was no variation in how individuals responded to the virus. Our survey proved the importance of these radiopharmaceuticals. We will expand on this knowledge to enhance the research that has already been conducted on the application of radiopharmaceuticals, and we will prioritise new features.
The process of scheduling was revealed to be reduced during the pandemic, this added support to the lack of staff and the reduced staffing levels. In addition, the use of certain radiopharmaceuticals was discontinued during the pandemic, which further supports the reduced pattern of purchasing. Similarly, Giammarile et al. 25 , also reported a significant reduction in nuclear medicine diagnostic and therapeutic procedures in June 2020 (73%) and October 2020 (56.9%) due to pandemic-related changes. The study also found that out of different nuclear www.nature.com/scientificreports/ medicine procedures, oncological PET tests, exhibited lower reduction in utilisation than the conventional nuclear medicine, especially nuclear cardiology. Moreover, in high-income nations, the detrimental effect was less evident. Gradually the situation of the supply chains of radioisotopes, generators and other essential materials is improving and showing the trend same as pre-Covid-19 time 25 . A European study reported that most of the European countries included in the study did not face any issue with the supply of radiopharmaceuticals 26 .
In the radiopharmacy lab, there was no standardised schedule to follow for the preparation of radiopharmaceuticals or specific uses. As reported by Moreira et al. 26 in most European nuclear medicine departments the most common organizational changes were alteration of scheduling practices, like rotating cohort teams of personnel to avoid widespread quarantine 26 . Additionally, the production schedule was modified to account for decreased demand resulting from staff reductions, fewer purchases, transportation issues, and additional hygienic precautions and regulations. COVID-19 impacted purchase orders, supply chains, how individuals work, and what they purchase. Numerous pandemics have been suggested to be cured by virtual reality [27][28][29][30] .
The regional lockdown, increased border controls, cancellation of most commercial passenger flights, and increases in cargo costs have reduced, delayed, or halted the availability and supply of vital medical radioisotopes. These radioisotopes are used in a variety of applications, including radiopharmacy, nuclear medicine, and research. This is true in light of the findings, which indicate that the supply and availability of these radioisotopes have been reduced, postponed, or completely halted 25,[31][32][33][34][35] .
A significant proportion of respondents followed the regional department's rules. More people were gathering information about COVID-19 via various social media platforms. This is similar to the findings of multiple studies that cited World Health Organization, National Energy Commission, and International Atomic Energy Agency [36][37][38][39] . According to the findings of this study, the rules regarding this pandemic need to be updated in order to remain inside the existing local regulations 40,41 . The guidelines for the clinical practise of nuclear medicine and radiopharmacy should be made available as soon as possible during COVID-19. This action will benefit the management of future COVID-19 variants such as late Delta and Omicron [42][43][44] .
We determined that the most efficient way for us to accomplish our goals here would be to conduct a simple local survey. We searched for and located basic data or databases that we could use to initiate this project. We discovered few relevant studies and surveys on COVID-19 for the radiopharmacy lab work of the nuclear medicine department. This created a challenge for us because we required more information on the subject. We have presented evidence in this survey that the nuclear medicine industry, lacks some kind of standardisation, particularly with regard to the surveys presented here. When we talk about standardisation, we're talking about a set of agreements or procedures that ensures a method or piece of work meets a standard. All relevant groups, divisions, service providers, and organisations in an industrial society must adhere to predetermined quality, agreement, uniformity, and comparability guidelines. This guarantees the success of design, production, and service.
The COVID-19 pandemic has had a significant negative impact on nuclear medicine therapeutics, clinical/imaging settings and research activities. Despite this significant impact, the researchers are embracing an attitude that "the show must go on". At the global level, the continuation of vital nuclear medicine services has been given priority. In the pandemic time, education on nuclear medicine was adapted. The research activity on nuclear medicine was not stopped during pandemic, rather the research activities continued significantly leading to emerging indications, innovative radiopharmaceuticals, and new imaging/data analysis techniques 45 .

Conclusions
According to the findings of this survey, COVID-19 made it difficult to conduct radiopharmacy business, duties, and activities, which hampered nuclear medicine research. The outstanding presence of 2-[ 18 F]FDG and 99m Tc-MAA radiopharmaceuticals during COVID-19 provide an opportunity and a scientific priority to study and research. There is a need for creative, quantitatively sound, and context-appropriate action plans. During and after the pandemic, standard regulations, instructions, patient care, recommendations, and protection should be implemented. There is currently a shortage of personnel in the highly specialised fields of nuclear medicine staffing and radiopharmacy, which may be responsible for at least some of the challenges. The number of people involved in radiopharmacy activities is expected to increase in the future. As a result, both the existence of a reliable information database and the standardisation of this process will be possible to avoid any other hurdles in the nuclear medicine and radiopharmaceuticals.

Data availability
The data are available within the paper. www.nature.com/scientificreports/