Radiation Protection in Medical Applications

Reducing Radiation In Medical Applications

By Nicholas Sion

The advent of nuclear medicine is advancing rapidly with the increasing popularity of using CT and SPEC scans for improved imaging and hence achieve desired results. The radiation dose from these scanners is now causing concern among patients and medical operating staff. Furthermore, radiopharmaceuticals are also being used in radiotherapy causing additional dose to the patient. Protective measures in reducing radiation dose are being researched and some current applications are described below.

In order to quantify the radiation we are exposed to, i.e. the resulting dose, and to assess its health impacts in perspective, it is necessary to establish its units where the basic unit of radiation dose absorbed in tissue is the Gray (Gy), where one Gray represents the deposition of one joule of energy on one kilogram of tissue. However, since neutrons and alpha particles cause more damage per Gray than gamma or beta radiation, another unit, the Sievert (Sv) is used in setting radiological protection standards. This unit of measurement takes into account the biological effects of different types of radiation. One Gray of beta or gamma radiation has one Sievert of biological effect, one Gray of alpha particles has 20 Sv effect and one Gray of neutrons is equivalent to around 10 Sv (depending on their energy).

Note that radiation in Sv or in Gy measurements are accumulated over time, whereas damage (or effect) depends on the actual dose rate, e.g. mSv per hour, per day or per year, or Gy per day as measured for radiotherapy.

But why do we fear radiation? because of its latency for cancer initiation and with the probability of genetic aberrations. It is cumulative and is very much dependant on the total dose received; yet has benefits when used therapeutically in measured doses.

Table 1 shows the increase of dose in medical applications when compared to other non-medical exposures. The ICRP [1] has publications on radiation protection in medical applications based on Risk-Benefit to the patient and optimized on the ALARA principle with doses commensurate with the medical purpose of the dose administered to the patient. For circulatory diseases (Cardiovascular and Cerebrovascular) the threshold is set at ~0.5 Gy. The time to develop cardiovascular and cerebrovascular fatality is >10 years.

What isotopes are used in nuclear medicine? They are indicated in Table 2 and are either reactor produced or cyclotron produced. For studying brain physiology and pathology Carbon-11, Nitrogen-13, Oxygen-15, Fluorine-18 are used in

PET scans. The F-18 in PET scans plays an important role in detecting cancers and for monitoring any progress in their treatment. From the above paragraphs and Tables it is clearly discerned that as more isotopes are used for diagnosis and for radiation therapy, such may reach a threshold where detrimental effects may arise to the patient and/or to the staff administering the therapy. Hence methods must be prescribed to reduce the received dose without compromising

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Acronyms, and Glossary ** are at end of this presentation

the treatment plan.

At the University of Sherbrooke [2], in vivo pre-clinical imaging is used on small animals with PET or SPECT scanners, supplemented by X-Ray CT scanners. Since these small animals host a large number of the human diseases, they can be studied under controlled conditions non-invasively then appropriate therapy can be extrapolated for size and weight, and then applied to humans in clinical therapy. As an example, the LD50/30** for a mouse is ~ 5-7.5 Gy. The recovery from residual radiation damage follows an exponential time course. If repeated, the sub lethal doses reduce the survival time (in a mouse by ~ -7%/Gy). Extrapolated and applied to humans, a dose of <1 Gy induces some blood cell destruction and releases free radicals. Doses of 5-200 cGy induces cell resistance to subsequent therapeutic radiation i.e. adaptive response. However, doses of 1-20 cGy have been reported to induce therapeutic effects in tumor cells. This procedure optimizes the dose to the individual patient.

Size Specific Dose Estimates (SSDE), where phantoms are used Fig. 1, is an alternative metric for better estimation of doses from CT scans in pediatric cases. Here, the dimensions of the children are considered and comparisons made between SSDE and **CTDIvol. Compared to SSDE, CTDIvol has underestimated the dose received in 91% of chest examinations for all abdomen-pelvis examinations. In summary, CTDIvol leads to false estimates and misinterpretation of the radiation dose from CT scans; whereas SSDE is easy to calculate offering a more accurate evaluation of dose. [3].

CT scan optimization is another method to reduce the patients’ exposure to ionizing radiation, A study was carried out by the Centre for Clinical Expertise in Radiation Protection (CCER) to evaluate the functionality of CT scanners from 4 manufacturers [4], viz. from GE, Siemens, Toshiba, and Philips. The optimized protocols used by anatomy, were applied to viz. head exams, chest exams, and abdomen-pelvis exams. These procedures reduced the dose to the patient by 18-24% without degradation in image quality. The ensuing recommendations are to use Bismuth shielding as required, to use low dose protocols for follow-up exams and to be specific to children’s size and age.

The 16 slice CT scanners came into use in 2002 and enabled non-invasive coronary angiography. However, the procedure delivered a higher dose to the patient than by the invasive procedure, the margins being 10-20 mSv by CT scan, and 3-6 mSv for the invasive technique [5]. Statistics show that between 1993 and 2006 the U.S. population grew by 1% annually, yet the use of CT scans increased by nearly 10%; and the effective dose increased by almost 600% from 0.5 mSv to 3 mSv (1980-2006). Table 3 shows the radiation dose a patient receives from CT scans. More dose reduction work needs to be achieved in either the equipment or in the procedure.

Following the ALARA principle, dose reduction methodologies were instituted, such as CT scanners gantry rotation speed, the number of installed detectors, iodine concentrations, software modifications i.e. by iterative reconstructions and pharmacological protocols, by using beta blockers and nitric oxide. High quality examinations can now be achieved with a radiation dose of 1-6 mSv, which is an improvement.

Current knowledge on cancer initiation and its progression is that it initiates from chemical agents, radicals, and radiations that damage the DNA leading to mutations, excluding the hereditary factors. This is exacerbated by genomic instability to accelerate the accumulation of the mutations. The progression of cancer is also stimulated by radiation inflaming the surrounding normal tissue. This progression is shown in Fig.2. Hence, customized therapy is becoming increasingly prominent for breast cancer patients [6], knowing that:

1.  Radiation favors the passage of cancer cells from the mammary gland and increases their number circulating in blood stream.

1. Irradiated mammary glands stimulate the migration of cancer cells.

However:

1. Proliferation of cancer cells is reduced in the irradiated mammary glands.
2. But, the irradiated mammary gland favors the development of lung metastases.

The above hypotheses was verfied by irradiatinig the mammary glands of a Balb/c mice with 4 fractions of 6Gy at 24h intervals using a Gamma Knife. The glands were then implanted with breast cancer cells and tracked Fig. 3. The pre-irradiation increased the migration and quantity of cancer cells and the number of lung metastases as predicted. However, in conservative surgery and by using radiotherapy, the aim is at optimizing the long term results rather than eradicating all cancer cells.

The tendency now is to advocate the use of Intensity Modulated Radiation Therapy (IMRT) where radiation doses are delivered with precision without harming the surrounding cells by using 3-D CT scans, or with MRI imaging in conjunction with dose calculations.

Personalized medicine for cancer treatment can offer an alternative treatment plan to radio-sensitive individuals but would require genomic sequencing. It is known that exposure to ionizing radiation may cause double strand breaks in the DNA whose repair pathways are very complex. Regulating the repair pathways are the H2AX, ATM and the p53 proteins. However, there is a new candidate: the Foxo3A transcription factor. Tests on genetically matched mice showed that H2AX plays a role in the Foxo3A-regulated stress response whose deficiency would cause genomic instability and radio sensitization. Because of this linkage, it may potentially be used in nuclear medicine for screening radio sensitive individuals making a case for personalized medicine, where persons would have their genome sequenced and specialized treatment prescribed. Fig.4, [7]. There are already 30 genomic medical centres for personalized medicine in the USA. The FDA has also approved three drugs for personalized medicine for lung cancer, for cystic fibrosis, and for melanoma. However, genomic sequencing raises ethical issues when not relegated to a treatment plan and if used by insurance companies and/or by employers.

In the continuing effort to reduce dose to patients the question arises whether nuclear medicine examinations in pregnancy can be permitted, and what are the means to reduce exposure to the foetus. The answer is affirmative [8] if it is required to save the mother’s life with strong considerations of the potential risks to the foetus and with the possibility

of terminating the pregnancy (strong cultural and moral issues here). Efforts are usually made to explore alternatives using non-ionizing radiation, else by using smaller quantities of administered isotopes and extending the imaging time provided the patient can remain still during the procedure. Typical radiation doses to the foetus are shown Table 4

Most female patients are advised not to become pregnant for at least 6 months after radioiodine therapy.

Metastable Technetium Tc-99m, is the isotope of choice in imaging with approximately 30000 therapeutic scans per week (Canada), 400000 (USA) and 600000 (Global). It becomes an issue to keep a supply chain open to maintain its availability. Since our governing authorities are demising the reactor based Tc-99m, the other source of supply is the cyclotron route where plans are to have one cyclotron per ½ million population to satisfy Canadian needs. Methods of generating Tc-99m can be found in Canadian Nuclear Society Bulletin March 2011, Vol 32 #1, p.15 Update on Radioisotopes and Nuclear Reactors, and on p.18 Which Way Radioisotopes, both authored by N. Sion

Purity of Tc-99m is paramount because it adds to the patients’ dose [9]. Table 5 shows the excess dose attributed to the other isotopes of Technetium that are the impurities contributing to the dose. In reactor produced Tc-99m, isolation procedures should be developed to remove the 100Mo/99Mo and selected niobium isotopes, These impurities contribute to additional radiation to patients because of their longer half-life. US Pharmacopoeia sets limits on these impurities to 0.015% of the Tc-99m radioactivity, and not to exceed 0.05% of the other radionuclide impurities.

But building cyclotrons and/or Linacs have their own radiological issues as highlighted in a recent CNSC workshop (Sherbrooke PQ, May 2013). They need to be housed in bunkers with licenses to construct, operate and finally to decommission. The previous photon energy exemptions of 10 MeV has now been reduced to 1 MeV. Regulatory requirements are increasingly stringent on the effects of neutrons, electron radiation; and the emanating secondary radiation via scatter and leakage. The aim is for a dose of 1 mSv/y for a NEW (Nuclear Energy Worker) and 50 μSv/y for the general public. At the primary and/or secondary walls, the Instantaneous Dose Rate < 25 μSv/h and the Time Averaged Dose Rate at < 20 μSv/h are being met as per NCRP-151 guides.