Each year the Student and Young Professionals Committee organizes a student paper contest in conjunction with the CRPA annual conference. This contest is open to all students enrolled full-time in a Canadian college or university program related to the radiation sciences.

Three finalists are selected and are given the opportunity to present their work at the conference in a plenary session. Conference registration (including banquet) and three nights hotel accommodation are provided for all three finalists.

The presentations are judged at the end of the session, and the winner is announced during the awards banquet later that night. The winner is awarded the Anthony J. MacKay trophy and a $250 cash prize, and their paper is published in the CRPA Bulletin.

All students who enter the contest will be given a free one-year CRPA membership.

This year’s finalists

Bryce Nelson

PhD candidate in oncology, University of Alberta

High-yield cyclotron production of Pb-203 using a sealed Tl-205 solid target

Bryce obtained his BSc in chemical engineering from the University of Alberta and is currently a PhD candidate in oncology at Edmonton’s Medical Isotope and Cyclotron Facility and the Cross Cancer Institute. His research involves developing cyclotron radionuclide production and automated purification processes, as well as applying radionuclides for targeted cancer diagnosis and therapy. Bryce is currently the president of the University of Alberta Oncology Graduate Students’ Association.

Mackenzie Tigwell

MSc radiation sciences student, McMaster University

Factors Contributing to Ho-166/PLLA Microsphere Degradation

Mackenzie is completing her MSc in radiation sciences–medical physics at McMaster University. Her research focuses on holmium-based poly-lactic acid microsphere production at the McMaster Nuclear Reactor. She is an advocate of accessible science and participates in various nuclear communication outreach projects. She has published two books, A Guide to Radiation for the Everyday Scientist and ABCs of Nuclear Science, to explain these topics in plain language. Mackenzie served as a special events coordinator with Let’s Talk Science, where she organized several research symposiums including Let’s Talk Nuclear. She is passionate about the nuclear field and excited to grow her career in this industry. 

Nikhil S. Patil

MD candidate, McMaster University

Radiologists’ Ability to Identify Noise and Image Quality in Pediatric Phantoms at One Institution

Nikhil Patil is a medical student at McMaster University interested in radiology and radiation safety. He previously studied medical health informatics and physiology, and he has always been interested in the intersection of healthcare and technology. During medical school, he has authored over 15 articles published in peer-reviewed journals and hopes to continue contributing to the field of academic radiology.

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Abstracts

Entrants are required to submit an abstract of no more than 750 words on a topic that is related to some aspect of radiation. The topic is intentionally kept broad to encourage participation from a wide range of students. Following are the abstracts submitted by this year’s finalists.

 

High-yield cyclotron production of Pb-203 using a sealed Tl-205 solid target

Bryce Nelson, PhD candidate in oncology, University of Alberta

Coauthors

• John Wilson, Jan Andersson, and Frank Wuest, University of Alberta
• Jonathan Doupe, Alberta Health Services
• Michael Schultz, University of Iowa

Introduction

Nuclear medicine theranostics involves labelling a biological targeting vector first with a radionuclide for diagnostic imaging, followed by a particle-emitting radionuclide for targeted radionuclide therapy. Lead-212 (Pb-212, t_1/2 = 10.6 h) is a particularly attractive therapeutic radionuclide due to its payload of one α and two β^– particles in its decay chain and the rapid decay of its progeny to stable Pb-208.

A recent clinical trial (Delpassand et al., 2022) using [Pb-212]Pb-DOTAMTATE to treat metastatic neuroendocrine tumours resulted in an 80% overall patient response rate, significantly exceeding standard-of-care treatments. However, diagnostic scans to track Pb-212 therapy were performed with conventional fluorine-18 and gallium-68 radiotracers. This is suboptimal, as dissimilar chemistries between the diagnostic and therapeutic radionuclides could result in different radiopharmaceutical biodistribution, potentially leading to unintended α-irradiation of healthy tissues.

Pb-212 is ideally paired with the chemically identical lead-203 (Pb-203, t_1/2 = 51.9 h) to provide diagnostic SPECT imaging using the 279 keV (81%) gamma-photons emitted during Pb-203 decay. However, worldwide supply of Pb-203 is extremely limited since cyclotron Pb-203 production requires irradiating highly toxic thallium (Tl) material.  

Our objectives were to develop a high-yield Pb-203 cyclotron production route using isotopically enriched Tl-205 target material and the Tl-205(p,3n) Pb-203 reaction as an alternative to lower energy production via the Tl-203(p,n) Pb-203 reaction. A robust cyclotron target and efficient chemical purification process must be designed to maximize Pb-203 yield and purity for research and clinical applications, while maintaining stringent radiation and chemical safety given the significant hazards presented to the operators and cyclotron facility.

Methods

Our entire process was designed around preserving radiation and chemical safety. To reduce Tl contamination risk, we employed our patent-pending sealed cyclotron target design that is used to produce other radionuclides.

Tl-205 metal (99.9% isotopic enrichment) was pressed using a hardened stainless-steel die. High purity aluminum (Al) target discs (99.999%) were machined with a central depression and annulus groove. 

A Tl-205 pellet was placed into the central depression of the Al disc, and indium wire was laid in the annulus. An aluminum foil cover was then pressed on, cold welding the cover to the disc via the indium with an airtight bond. 

Targets were irradiated at 23.3 MeV for up to 516 minutes on a TR-24 cyclotron at proton currents up to 60 μA to produce Pb-203 via the Tl-205(p,3n)Pb-203 nuclear reaction. Following a period of >12 h to allow decay of Pb-204m (t_1/2 = 67 min, 899 keV [99%]), the target was removed and Tl-205 was dissolved in HNO₃. 

A NEPTIS Mosaic-LC synthesis unit performed automated separation using Eichrom Pb resin, and Pb-203 was eluted with HCl or NH₄OAc. The waste solution was diverted to a vial for subsequent Tl-205 recovery in an electrolytic cell. 

Pb-203 product radionuclidic and elemental purity were assessed by high-purity germanium (HPGe) gamma spectroscopy and inductively coupled plasma optical emission spectroscopy (ICP-OES), respectively. Radiolabelling and stability studies were performed with PSC, TCMC, and DOTA chelators, and Pb-203 incorporation was verified by radio-TLC analysis.

Results

 Cyclotron irradiations were performed at a 60 μA proton beam current and 23.3 MeV energy without any target degradation. Automated purification took <4 h, yielding >85% decay-corrected Pb-203 with a radionuclidic purity of >99.9%. Purified Pb-203 yields up to 12 GBq were attained, and Pb-203 was successfully chelated and exhibited >99% incorporation after 120 h in human serum. 

Radiation safety implications: In over 100 production runs, there were no cyclotron target station or processing equipment contamination incidents. 

Targets were irradiated during the afternoon and removed the following morning to permit decay of short-lived impurities. By allowing >12 hours (>10 Pb-204m half-lives) prior to target removal, operator dose was minimized. 

Utilizing high purity Al target components nearly eliminated long-lived activation products, minimizing operator extremity dose when performing target recycling. When combined with a target retrieval shielding cart, a custom-designed lead-shielded processing castle, and an efficient automated process, the operator radiation dose per full production run is <10 µSv (measured by electronic personal dosimeter). 

Conclusion

Our recently published high-yield Pb-203 production process significantly enhances Pb-203 production capabilities to meet the rapidly growing worldwide preclinical and clinical demand for Pb-203 radiopharmaceuticals alongside Pb-212 alpha particle therapy. 

Since January 2022, we have successfully shipped over 60 batches of Pb-203 to customers and collaborators in 11 locations across 5 countries for research and diagnostic SPECT imaging clinical trials of metastatic melanoma and neuroendocrine tumours. Although we anticipate continually increasing demand, we are confident that our robust process design will maintain operator radiation dose at a small fraction of the permitted annual limit.

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Factors Contributing to Ho-166/PLLA Microsphere Degradation 

Mackenzie Tigwell, MSc radiation sciences student, McMaster University

Coauthor

• Andrea Armstrong, research scientist, McMaster Nuclear Operations and Facilities, and adjunct assistant professor, McMaster University

Background

Selective internal radiation therapy (SIRT) has been gaining popularity as a treatment for hepatocellular carcinoma. A beta-emitting isotope is encapsulated in microspheres and injected into the liver via the hepatic artery. Initial treatment options used Y-90 encapsulated in aluminosilicate glass (Barros et al., 2014). Y-90 undergoes pure beta-minus decay with a 64.1 hour half-life. This results in concentrated doses of radiation directly at tumor locations and minimal external dose risk to manufacturing staff, administering physicians, and shielding requirements to ship treatments. However, Y-90 microspheres do not allow for any imaging to track the location of microspheres. Due to this major limitation, other isotopes were considered for selective internal therapy treatments.

Holmium-166/PLLA microspheres can be used for SIRT while remaining imageable via MRI or SPECT (Yamazaki et al., 2020). Ho-166 decays 100% via beta-minus decay followed by gamma ray emissions of 80 keV (6.5%) and 1379 keV (0.9%). Due to Ho-166 half-life of only 26.8 hours, higher specific activity is needed at production. The gamma emissions and higher specific activity cause radiation dose risk to production staff. Additionally, PLLA microspheres are staticky and act like a powder, unlike previous glass versions. This presents additional radiation protection challenges.

There are several considerations during the production and suspension of Ho-166/PLLA microspheres to ensure adequate quality for patient treatment. Neutron irradiation causes damage to microspheres leading to decomposition. This damage is theorized to be caused by temperature, gamma photons, fast neutrons, and/or side reactions of thermal neutron capture (Vente et al., 2009).

Methods

Microspheres were exposed to a range of gamma doses (0 kGy to 800 kGy) using a cobalt-60 source. The microsphere batches were then divided and maintained at temperatures ranging from 20°C to 100°C for at least 4 hours. This created samples with unique combinations of temperature and gamma radiation exposure. 

To assess environmental factors in-core, a rig with detachable Pb shielding was engineered. Shielding of 0.25 cm to 1.25 cm were tested for temperature, flux, and sample quality. Microspheres were tested at specific activities ~25 MBq/mg and ~40 MBq/mg.

All samples were suspended in media and imaged at 24-hour intervals. Sample quality was assessed by light microscope imaging with a digital camera attachment. The total number of damaged microspheres was calculated as a percentage of the total. 

Results

Temperature showed significant impact on quality. Batches below 55°C had minimal damage (~1% to 4%). The 60°C and 65°C samples represented a significant damage threshold, where damage was at least 2x that of a control sample at suspension (6% to 20%). A damage threshold of 60°C to 65°C coincides with the glass transition temperature (Tg) of PLLA. The 70+ °C batches had extreme levels of damage in all samples, in the range of 80% to 100% damage.

Gamma dose in temperatures below Tg did not show any notable impact on quality except for 600 kGy samples. Samples at 600 kGy showed more damage than 800 kGy samples in almost all trials. The effects of gamma radiation seen in these trials may change for increased dose rates, more representative of environments in-core. Notably, batches exposed only to gamma radiation and temperature did not show degradation over time, normally seen in samples irradiated in-core.

Variable shielding in core had prominent impacts on temperature, neutron flux, and sample quality. The temperature in the rig showed a decreasing trend with the increase of Pb shielding. Temperatures exceeded 60°C in the 0.25 cm shield but dropped to 43°C by the 1.25 cm attachment. Thermal neutron flux decreased with greater Pb thickness for attachments of 0.25 cm to 1.0 cm. The 1.25 cm shield increased thermal neutron flux. Microsphere samples in attachments 0.25, 0.5, and 0.75 were all viable at ~25 MBq/mg. Microsphere samples at ~40 MBq/mg showed unacceptable damage in attachments 0.25 cm to 1.0 cm of PB.

Conclusions

Temperature showed the most drastic impact on quality. The 60/65 °C samples represented a significant damage threshold. This temperature coincides with the glass transition temperature (Tg) of PLLA, which falls in the range of 60°C to 65°C. Ionizing radiation inducing chain scissions reduces Tg and may account for the increasing damage in samples above 200 kGy heated to 65°C. Gamma dose had minimal impact on low temperature samples. Samples irradiated to 600 kGy had more severe damage than other batches and suggests a damage threshold induced by polymer chain-scissions. Further testing is needed for dose-rate impact. Finally, increased Pb shielding of samples was shown to decrease temperature in the sample chamber and alter the thermal neutron flux. These insights inform the selection and equipment production of new reactor sites for Ho-166/PLLA microsphere production. 

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Radiologists’ Ability to Identify Noise and Image Quality in Pediatric Phantoms at One Institution

Nikhil S. Patil, MD candidate, Michael DeGroote School of Medicine, McMaster University

Coauthors

• Scott Caterine, Department of Radiology, McMaster University
• Chris Gordon, Department of Radiology, McMaster University
• John Donnellan, Department of Radiology, McMaster University

Introduction

Pediatric patients exposed to radiation due to diagnostic imaging have an increased risk of developing future malignancies. Radiology scanning procedures and technology vary from institution to institution, making it difficult to come up with universal strategies for radiation dose reduction. We conducted a single-institution study investigating the ability of radiologists to detect changes in imaging noise and diagnostic quality at different radiation doses in pediatric phantom scans.

Methods

One pediatric “phantom” patient of a simulated head, chest/abdomen/pelvis, and abdomen/pelvis was scanned using computed tomography at four different noise index levels. Each image set was scanned four times to create four different series, with each series having a different noise index level. To modify the noise index between image sets, the mAs was modified between each series.

Radiologists at our institution were surveyed for determining relative noise, identifying scans closest to the current standard of practice, and determining scans of diagnostic quality.

Results

Ten radiologists were surveyed. The included participants were academic staff radiologists at McMaster University with five to 28 years of experience practising radiology. Six of the included radiologists were pediatric subspecialists, whereas the remaining four were adult radiologists. Similarly, the time spent reporting pediatric specific scans was widely variable, ranging from every day to rarely ever.

Overall, the included participants were able to correctly rank 104/160 series when asked to order the series from least noise to most noise. 

• 33/40 responses stated that more than one series were of equal noise, which was not true in any of the phantom scans. 
• 11/40 responses stated that the series with the most noise was of diagnostic quality.
• 9/40 of responses correctly identified the series most similar to their current standard of practice.

There was variability in classification accuracy for relative noise between the abdomen/pelvis, chest/abdomen/pelvis, and head scans. Similarly, there was variability in the classification accuracy between the pediatric and adult radiologists.

Discussion

This quality improvement study found that, in general, there was considerable variability in radiologists’ ability to accurately determine the relative noise index of a scan when comparing it to the same scan of a different noise index, as radiologists were only able to correctly rank series from least noise to most noise 60% of the time (104/160). 

Furthermore, this study showed that many radiologists report series with a NI higher than the institution standard were of diagnostic quality. This indicates the potential for increasing the noise index in order to reduce radiation dose, without losing diagnostic quality of that image.

Our institution-specific findings are consistent with the literature in that the ability for radiologists to accurately discern scans with higher noise from those with lower noise displays interobserver and international variability. 

Interestingly, classification accuracy for relative noise appeared to vary between the abdomen/pelvis, chest, and head scans.

When asked what series was most similar to radiologists’ current standard of practice, there appeared to be a tendency to pick the series with the least noise. Additionally, multiple radiologists found scans to be of equal noise index, when in reality none of the scans had the same level of noise. This strengthens the possibility for increasing the noise index for the purpose of reducing pediatric radiation dose without sacrificing diagnostic quality.

Further investigation is warranted with regards to reducing radiation doses without sacrificing diagnostic quality. Eventually, conducting a similar study with patients would provide the highest quality evidence. Furthermore, we highlight the importance of conducting institution-specific dose reduction studies to improve radiation exposure practices at the institution level, and beyond.

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See related articles:

2022 Anthony J. Mackay Student Paper Contest Winners, February 16, 2023

2019 Anthony J. MacKay Student Paper Contest, June 7, 2019

2018 Anthony J. MacKay Student Paper Contest, May 8, 2018