Lead Shielding Research Articles

Whole body potassium as a biomarker for potassium uptake using a mouse model

Potassium is known for its effect on modifiable chronic diseases like hypertension, cardiac disease, diabetes (type-2), and bone health. In this study, a new method, neutron generator based neutron activation analysis (NAA), was utilized to measure potassium (K) in mouse carcasses. A DD110 neutron generator based NAA assembly was used for irradiation.Thirty-two postmortem mice (n= 16 males and 16 females, average weight 22.02pm 1.3 and 17.9pm 1.1 g) were employed for this study. Soft-tissue equivalent mouse phantoms were prepared for the calibration. All mice were irradiated for 10 minutes, and the gamma spectrum with 42K was collected using a high efficiency, high purity germanium (HPGe) detector. A lead shielding assembly was designed and developed around the HPGe detector to obtain an improved detection limit. Each mouse sample was irradiated and measured twice to reduce uncertainty. The average potassium concentration was found to be significantly higher in males (2846 pm 525 upmu g/g) compared to females (2116.2 pm 432 upmu g/g). We also observed a significant correlation between potassium concentration and the weight of the mice. The detection limit for potassium quantification with the NAA system was 46 ppm. The radiation dose to the mouse was approximately 56 { pm 1.6 } mSv for 10-min irradiation. In conclusion, this method is suitable for estimating individual potassium concentration in small animals. The direct evaluation of total body potassium in small animals provides a new way to estimate potassium uptake in animal models. This method can be adapted later to quantify potassium in the human hand and small animals in vivo. When used in vivo, it is also expected to be a valuable tool for longitudinal assessment, kinetics, and health outcomes.

In soil measurement of radiation dose caused by X‐ray computed tomography

AbstractRadiation damage to plants through X‐ray exposure has been reported to impair root growth. The literature on the critical dose for growth impairment is inconclusive, partly as dose measurements in soil are scarce. Here we fill this gap and show that the dose in a typical single pot scan amounts to 1.2 Gy. In addition, we demonstrate the shortcomings of estimating the dose from scan settings using the RadPro Calculator and highlight the efficient reduction of X‐ray exposure by a lead shield.

Technique, Time Demand, Radiation Exposure, and Outcomes of Skin-anchored Intraoperative 3D Navigation in Minimally Invasive Posterior Cervical Laminoforaminotomy.

This was a retrospective review. The objective of this study was to describe our technique and evaluate the time demand, radiation exposure, and outcomes of minimally invasive posterior cervical laminoforaminotomy (MI-PCLF) using skin-anchored intraoperative navigation (ION). Although bone-anchored trackers are most commonly used for ION, a novel technique utilizing noninvasive skin-anchored trackers has recently been described for lumbar surgery and has shown favorable results. There are currently no reports on the use of this technology for cervical surgery. Time demand, radiation exposure, and perioperative outcomes of MI-PCLF using skin-anchored ION were evaluated. Twenty-one patients with 36 operative levels were included. Time for ION setup and operative time were a median of 34 and 62 minutes, respectively. Median radiation to the patient was 2.5 mGy from 10 seconds of fluoroscopy time. Radiation exposure to operating room personnel was negligible because they are behind a protective lead shield during ION image acquisition. There were no intraoperative complications or wrong-level surgeries. One patient required a repeat ION spin, and in 2 patients, ION was abandoned and standard fluoroscopy was used. Skin-anchored ION for MI-PCLF is feasible, safe, and accurate. It results in short operative times, minimal complications, low radiation to the patient, and negligible radiation to operating room personnel.

Contamination Measurements from Simultaneous Activated Potassium Bromide Radiological Dispersal Devices with a Collimated Vehicular Sensor.

Surface contamination was quantified over a distributed source of activated potassium bromide from three detonations of Radiological Dispersal Devices (RDDs) at the Idaho National Laboratory Radiological Response Training Range, with a maximum sampled area of 19,900 m2, to provide a baseline comparison with other rapid, remote mapping methods. Measurements were obtained with a cerium bromide sensor collimated to a field of view of 3.14 m2, using lead shielding, and towed behind a ground vehicle. Sensor response correction factors for activated potassium bromide were calculated through simulation with SWORD to obtain activity per meter-squared. Continuous maps were produced by interpolating coverage from lawnmower raster scans. Radiological data was overlaid with aerial imagery from an automated unmanned aerial vehicle flight to provide contextual geological information relative to contamination levels. The contamination distribution measurements will be compared to unmanned aerial vehicle methods in future work.

High-precision measurements of half‐lives for 69Ge, 73Se, 83Sr, 85mSr, and 63Zn radionuclides relevant to the astrophysical p-process via photoactivation at the Madison Accelerator Laboratory

The ground state half-lives of 69Ge, 73Se, 83Sr, 63Zn, and the half-life of the 1/2− isomer in 85Sr have been measured with high precision using the photoactivation technique at an unconventional bremsstrahlung facility that features a repurposed medical electron linear accelerator. The γ-ray activity was counted over about 6 half-lives with a high-purity germanium detector, enclosed into an ultra low-background lead shield. The measured half-lives are: T1/2(69Ge) = 38.82 ± 0.07 (stat) ± 0.06 (sys) h; T1/2(73Se) = 7.18 ± 0.02 (stat) ± 0.004 (sys) h; T1/2(83Sr) = 31.87 ± 1.16 (stat) ± 0.42 (sys) h; T1/2(85mSr) = 68.24 ± 0.84 (stat) ± 0.11 (sys) min; T1/2(63Zn) = 38.71 ± 0.25 (stat) ± 0.10 (sys) min. These high-precision half-life measurements will contribute to a more accurate determination of corresponding ground-state photoneutron reaction rates, which are part of a broader effort of constraining statistical nuclear models needed to calculate stellar nuclear reaction rates relevant for the astrophysical p-process nucleosynthesis.

Increased lead concentrations in the hairs of radiographers in general hospitals

This study investigated lead concentrations in the hairs of radiographers working in the radiological departments of general hospitals that used lead shielding for radiation protection. We collected scalp hair samples from 32 radiographers working in four radiology departments with lead shielding and 18 administration personnel in the same hospitals without lead shielding. Samples were analyzed for lead concentrations by inductively coupled plasma mass spectrometry. As a result, lead concentrations in the hairs of the radiological technologists were significantly higher than those in the administration staffs (0.72 ± 0.51 vs. 0.19 ± 0.27 μg/g, P < 0.001). The hair lead concentrations were positively and significantly associated with environmental lead concentrations (r = 0.6, P = 0.001), but not associated with age, working duration, and gender distribution.

An alternative to the use of lead for patient treatment shielding in superficial radiotherapy.

Lead shielding is commonly used in the delivery of superficial radiotherapy albeit that the toxicity of this substance is of concern. The feasibility of using a non-toxic alternative, AttenuFlex™, is assessed using Xstrahl and Sensus treatment units. A series of lead and AttenuFlex™ circular cut outs and applicators were used with superficial beams (1.0-8.5mm Al HVL) to measure percentage depth dose (PDD), output factors (OF) and surface dose correction factors (DCF). X-ray transmission for each material was determined for each beam quality. For these measurements an Advanced Markus chamber either embedded within a virtual water phantom (PDD, OF, transmission) or placed on the surface of the phantom with entrance window downstream (DCF), was used. The depth of the phantom is 10cm for PDD and surface OF measurements. DCF(t) measurements were obtained with underlying lead or AttenuFlex™ at depth t = 0.1-10cm. Additionally, using EBT3 film fluorescent surface doses, to non-target tissue, due to underlying lead or AttenuFlex™ were compared.PDDs and OFs for both materials were within ± 1%. Lead and AttenuFlex™ transmission differences were clinically acceptable, all transmission values were < 5% and non-target doses were comparable. The variation of DCF(t) for lead and AttenuFlex™ exhibit a minima for all beams. In the minima region energy and applicator dependent differences between DCF(lead) and DCF(AttenuFlex™) are observed. These differences do not preclude the use of AttenuFlex™ as an alternative to lead in superficial therapy.

High resolution measurements with miniature neutron scintillators in the SUR-100 zero power reactor

Three 1-mm3 miniature fiber-coupled scintillators have been used to perform cm-wise resolution measurements of the thermal neutron flux within experimental channels of the SUR-100 facility, a zero power thermal reactor operated by the Institute of Nuclear Technology and Energy Systems at the University of Stuttgart. The detection system is developed at the École Polytechnique Fédérale de Lausanne in collaboration with the Paul Scherrer Institut. Thermal neutrons count rates were measured along the experimental channels I and II, which cross the reactor at the center and tangentially to the core, respectively. The reactor was modelled with the Monte Carlo neutron transport code Serpent-2.1.31. The comparison of experimental and computed reaction rate distributions showed a good agreement within the core region, with discrepancies within 2σ. An unexpected discrepancy, probably caused by a geometric inconsistency in the computational model of the reactor, was observed in the reflector region of the experimental channel I, where a 20% difference (i.e. 8σ) was found between experimental and simulated results. Significant discrepancies, respectively worth 10σ and 15σ, were noticed at distance, in the lead shielding region, for both experimental channels I and II. In addition, reaction rate gradients across the 2.6 cm and 5.4 cm diameters of both channels were measured. A horizontal reaction rate gradient of (9.09 ± 0.20) % was measured within 2.4 cm across the diameter of the experimental channel II, with a difference from computed results of 2%. The absence of a vertical reaction rate gradient inside the experimental channel I was confirmed by measurements.

Sensitivity and low-energy response of the Small Anode Germanium well detector with ceramic insert

A Small Anode Germanium (SAGe) detector was recently installed in the Shallow Underground Laboratory (SUL) at Pacific Northwest National Laboratory (PNNL). The unique electrode structure and the short signal wire length in the detector guarantees superior energy resolution than traditional well detectors. The detector is inside an ultra-low background graded lead shield and is fitted with a CosmicGuardTM cosmic veto background reduction system. In this work, the capabilities of this SAGe well detection system were explored using samples with broad characteristics (a Heisenberg cube and individual samples containing 161Tb and 140Ba). The results demonstrate impeccable sensitivity of the system to resolve low-energy complex spectra and provide trustworthy activity estimates by correcting for cascade summing effects.

Development of an end-effector system for autonomous spraying applications and radiation surveying

This paper presents the design and testing of a scale proof-of-concept prototype robotic end-effector system for autonomous robotic shotcrete application and radiation surveying in underground uranium mining environments. The system presented consists of two functionally distinct prototype tools that achieve the independent tasks of autonomous robotic spray pattern control and surface radiation surveying. The first prototype tool presented is a novel, robotic shotcrete spraying tool that is capable of autonomously maintaining and adjusting its circular spray pattern diameter on target surfaces in response to changes in target surface distance. Control algorithms are presented that give the robotic shotcrete spraying tool the capability to produce advanced figure eight and spiral spraying patterns for surface preparation applications that involve spot filling deep surface cracks and pockets. Physical testing of the prototype tool empirically verified its ability to maintain circular spray pattern diameters at various target distances and demonstrated the application potential of the advanced figure eight and spiral spraying patterns. The second prototype tool presented is a Geiger–Müller tube-based radiation detection tool that uses lead shielding and a single-hole collimator in combination with precise robotic positioning to capture localized radiation measurements of surfaces within radiation-rich environments. Physical testing of the prototype tool demonstrated its ability to create radiation survey profiles that distinctly characterized the radiological profile of test target surfaces embedded with various radioactive sources.

Inhalation anesthesia and shielding devices to allow accurate preclinical irradiation of mice with clinical linac-based systems: Design and dosimetric characteristics

This technical note describes two devices to enable accurate irradiation of mice on clinical linac-based systems. To study the effects of radiation in murine, preclinical animal models, controlled and accurate dosing is important. This is not only important when specific volumes need to be irradiated, but also when the whole animal body is irradiated. To enable both purposes, we designed two devices. One device to administer Total Body Irradiation (TBI) simultaneously to six, free walking mice, and a second device, denoted as target box, in which we irradiate specific parts of the mice whilst organs-at-risk (OAR) are protected. In this latter device, we can position the mice in multiple ways. One configuration allows to sedate twelve mice simultaneously by isoflurane inhalation anesthesia and protect the body by lead shielding to allow radiation of the head only. Alternatively, the target box can be used to sedate maximal 4 mice simultaneously to irradiate the flank or paws only. All these setups allow high experimental throughput and thus a minimal occupation of the clinical equipment. As measured, the delivered radiation dosages in the regions of interest were accurate for both devices. In this technical note, we describe the design and build of these devices.

STUDIES OF THE INFLUENCE OF THE LEAD SHIELDING GEOMETRY ON THE GAMMA SPECTRA MEASURED BY THE LOW BACKGROUND SPECTROMETER SYSTEM USING THE HPGE DETECTOR

In the measurement of gamma spectra by the low background gamma spectrometer system using the HPGe detector, lead shields have been often used for preventing from gamma rays in background radiation. Rely on the laboratory facilities, lead shielding geometry can be different. Gamma rays from the measured radioactive source interact with matter as the lead shield, then enter the HPGe detector and contribute the backscattering area of the gamma spectrum. Basing on that, this work presents estimating the influence of the lead shielding geometry on the gamma spectra. The MCNP5 code was used to simulate the gamma spectra of 137Cs, 54Mn, 60Co and 22Na measured by the gamma spectrometer system with the lead shield having cylinder or square prism shape. The effectiveness of simulation modelling based on the MCNP5 code was validated by comparison of experimental and calculated gamma spectra. The results showed that using the lead shield shaped cylinder, backscattering gammas contribute from 3.68% to 5.23% more than using the lead shield shaped square prism.

Efficiency of non-lead and lead thyroid shields in radiation protection of CT examinations

BackgroundThyroid dose reduction during brain CT scan procedures, using protective lead clothing such as lead thyroid collars were approved in the last decades. Recently, investigators have focused on applying and designing light and non-toxic shields that contain no lead. ObjectiveThis study aimed to compare the efficiency of non-lead and lead thyroid shields in radiation protection during brain CT scans based on Monte Carlo (MC) simulation and experimental measurements. MethodsThis study was performed in two steps. The first step was the MC simulation of a different combination of shielding materials to assess the efficiency of X-ray attenuation in these shields. The second step was the construction and testing of the shield, which was more efficient in MC calculation as a thyroid shield in brain CT scan. The absorbed dose of a Rando phantom thyroid was determined by both non-lead and lead shields as thyroid protectors. The thyroid radiation dose was measured with and without the usage of radiation shields. The percentage difference between the dose in the presence of the shield and without the shield was calculated. ResultThe percentage difference of the surface radiation doses on thyroid location with non-lead (combination of 45% Tungsten- 55% Tin) and lead shields in comparison to without application of the radiation shield were 35.88% and 20.73, respectively. The dose reduction at the depth of the thyroid was 39.79% and 21.49% applying non-lead and lead shields, respectively. ConclusionAccording to the results, the use of non-lead shield can reduce the absorbed dose of thyroid more efficiently than the lead shields.

Effect of protective glasses on radiation dose to eye lenses during whole breast irradiation.

ObjectivesThe efficacy of radiotherapy for breast cancer has greatly improved owing to better irradiation methods. Radiotherapy aims to deliver therapeutic doses to predetermined target volumes while sparing surrounding healthy tissues. However, there are few reports on radiation exposure to eye lenses, and the recommended exposure limits to ocular lens have been substantially reduced in recent years. This study aimed to investigate the amount of radiation exposure to eye lenses using optically stimulated luminescence dosimeters (OSLDs) and determine whether wearing special protective devices to protect the eyes, as an organ at risk, during whole breast irradiation, is necessary.MethodsThis experiment used OSLDs on water‐equivalent phantom to measure the change in scattered radiation dose due to the difference of irradiation field while using 4‐ and 6‐MV photons of TrueBeam linear accelerator. Using a total treatment dose of 50 Gy, a target was positioned to approximate the breast, and a plan was formulated to deliver 2 Gy per treatment by tangential irradiation. The mean (SD) irradiation dose at the lens position outside the irradiation field was reported.ResultsThe scattered radiation dose outside the irradiation field was more affected by the irradiation field size than by the radiation energy. The out‐of‐field irradiation dose with a larger field of view was higher than that with a smaller field of view. The use of 0.07‐ and 0.83‐mm‐thick lead shield protective glasses reduced the radiation dose by 56.1% (P < .001) and 55.6% (P < .001), respectively.ConclusionsIn this experimental model, the amount of radiation the eye was exposed to during whole breast irradiation was determined by the distance of the eye from the radiation field edge and by wearing protective glasses. In clinical practice, the protection offered by eyeglasses may reduce the risk of long‐term side effects and allow the use of higher intensive radiotherapy.

Impacts of gamma ray emissions of materials containing 232U on safety, security, and safeguards

The introduction of 232U to uranium materials is a possible technique to reduce the material attractive of the material for weapons purposes. In order to implement 232U in civilian nuclear fuel cycles, its impacts on safety, security, and safeguards must be considered. This study will utilize an initial mixture of 0.03 at.% 232U with natural uranium, enriched to approximately 3, 5, 20, and 90 at.% 235U. The mixture with natural uranium, 3, 5, and 20 at.% 235U represent uranium isotopic vectors that would be commonly found within civilian nuclear fuel cycles. The 90 at.% 235U isotopic vector represents weapons grade uranium. The security and safeguards results from each isotopic vector will be compared to results from a corresponding isotopic vector that does not contain 232U, but has the same 235U/238U ratio. Considering 232U’s daughter products contribute significantly to the gamma ray emissions over time, the isotopic vectors will be evaluated at three time intervals: fresh, 0.5 year, and 10 years. When compared to standards put in place by U.S. Nuclear Regulatory Commission, the dose rates produced by the uranium isotopic vectors containing 232U indicate the need for additional safety protocol to shield workers from this increased dose rate. These gamma ray emissions produce a significant increase in detectability in the weapons grade uranium isotopic vector with 232U even in the presence of lead shielding. A common safeguards technique used to verify 235U enrichment was shown to be useless in the presence of 232U and its daughter products. This would require the use of a different technique in order to verify the 235U enrichment.

A novel approach to embed eye shields in customized bolus on nasal dorsum treatment for electron radiotherapy

We aim to demonstrate the unique use of embedded lead eye shields in an electron wax bolus when treating the nasal dorsum. A patient presented to the clinic with squamous cell carcinoma of the nasal dorsum requiring treatment with en face electrons. A 3D customized wax bolus was designed and imported into the treatment planning system (TPS) to calculate the dose distribution. Due to high lens dose, the bolus was customized further to create 2 milled open slots in the wax, over the lens of eye, to allow lead sheets totaling 4 mm to be slid into the wax. The patient was brought back to the clinic to be scanned with the wax bolus fitting snugly over the nose, eyes, and cheek regions. The 3D milled insert holes were contoured on the CT in the TPS, assigned HU of 2758, to mimic the lead insertion. The lens dose with lead inserts was compared to the plan without lead insert. To further confirm the lens dose, EBT3 films were placed on the right and left eye under the bolus, and nose dorsum on the first day of treatment. The maximum dose of right lens, as calculated in the TPS with the simulated lead shields in place, decreased from 989.5cGy to 457cGy. The maximum dose of left lens decreased from 1085.4cGy to 501cGy. The dose readings from EBT3 films were in good agreement with the TPS, with deviation of 3.32%, 0.26%, and 3.44% for right lens, left lens, and nose, respectively. Daily positioning deviations compared to the plan were 0.65 ± 0.16cm and 0.63 ± 0.29cm for right eye and left eye, respectively. This novel device demonstrated the feasibility, in terms of dose calculation accuracy in the TPS and fabrication, of using customized bolus with lead inserts to conveniently shield the lens of the eyes in an electron treatment for the nose, enabling a streamlined daily setup.

Design, construction and characterisation of a portable gamma-ray spectrometer for low-level natural occurring radioactive material ex-situ measurement

The activity concentrations in naturally occurring radioactive material (NORM) samples are conventionally measured using a gamma-ray spectrometer with a single detector (mostly HPGe or NaI:Tl) enclosed in a lead shield. In this work, a passive water shield to reduce background radiation reaching the detectors was designed using GEANT4-toolkit Monte Carlo simulations and then constructed. This measurement system is portable and cost-effective for ex-situ measurements. IAEA-375 soil and beach sand each placed in Marinelli beakers were measured using two LaBr3:Ce detectors in singles and coin-cidence modes. A novel method of background reduction by using photon time-of-flight was employed together with the measurement of the two photons energies. These samples were also measured in singles mode using a NaI:Tl detector inside the constructed water shield and HPGe detector shielded with lead to compare and validate the results of LaBr3:Ce detectors measurement. Both the simulated and measured results show that the water shield (500 mm thick) attenuates 2614.5 keV gamma rays by 90 %. The minimum detectable activity (MDA) measured for 24 h using the NaI:Tl detector without shield and inside the water shield are; 546 Bq kg−1 and 146 Bq kg−1 at 1460.8 keV (40K), 194 Bq kg−1 and 15 Bq kg−1 at 1764.5 keV (238U series), and 131 Bq kg−1 and 15 Bq kg−1 at 911.2 keV (232Th series), respectively. The measured activity concentrations of 238U and 232Th series and 40K radionuclides inside IAEA-375 soil agree with certified values to within measurement uncertainties. The measured activity of 138La in the LaBr3:Ce detector crystal is 263.8 ± 26.8 Bq kg−1. The internal activity of the LaBr3:Ce detector increases the MDA at 1460.8 keV and 2614.5 keV, which limits the measurement of primordial radionuclides with low activity concentration in singles mode. The activity concentrations of 238U and 232Th series radionuclides in beach sand were measured using NaI:Tl and LaBr3:Ce detectors. The results are consistent with those from HPGe measurement to within uncertainties.

P104. A review of time demand, radiation exposure and outcomes of skin-anchored intraoperative 3D navigation in minimally invasive posterior cervical laminoforaminotomy

BACKGROUND CONTEXT Real time image-guidance and intra-operative 3-dimensional navigation (ION) are increasingly being utilized in spine surgery to provide better visualization, improve accuracy and enable less invasive procedures. Studies have shown effective early adaption and radiation reduction with this technology in minimally invasive lumbar spine surgery. However, the novel use of a noninvasive skin-anchored tracker has not yet been described for cervical spine surgery. PURPOSE To describe the time demand, radiation exposure and outcomes of ION using a skin-anchored tracker in minimally invasive posterior cervical laminoforaminotomy (MI-PCLF). STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE All patients who underwent MI-PCLF by a single surgeon from April17-November 19. OUTCOME MEASURES Time for navigation set-up, operative time, estimated blood loss (EBL), radiation exposure to operating room (OR) personnel and the patient, complications and length of stay. METHODS Operative variables, radiation exposure and perioperative outcomes were summarized using descriptive statistics. RESULTS Twenty-one patients (36Levels) with a mean age of 55+11.79yrs, BMI of 27.36+2.95kg/m2, and comprising 17(81%) males were included. A majority of cases were 1-level (9; 42.9%) or 2-level (10; 47.6%), with only one 3-level and one 4-level surgery. The operative levels were: C3C4 (11.1%), C4C5 (19.4%), C5C6 (22.2%), C6C7 (25%), C7T1 (22.2%). Time required for ION set-up, measured as the time from end of anesthesia induction to the start of the surgical procedure was a median of 34 mins [IQR 30-37]. This accounts for the time required for patient positioning, preparing and draping the incision site, placing the skin-anchored navigation tracker and acquiring a 3D image for real-time navigation. The total fluoroscopy time was a median of 10 sec [IQR 9-11], almost entirely attributable to ION image-acquisition; and radiation dose was a median of 2.5mGy [IQR 1.8-4.9]. Thus, radiation exposure to the patient was minimal. Since all OR personnel are behind a protective lead shield during ION image-acquisition, radiation exposure to the surgeon and OR team was negligible. One patient required a repeat ION spin, resulting in the fluoroscopy time for ION image-capture being 20sec. In two patients, ION was abandoned and the procedure was completed using fluoroscopy resulting in the total fluoroscopy time being 17&27sec (9sec for ION spin; rest for fluoroscopic guidance). Additionally, one patient had a radiation dose of 13.9mGy, which is almost three times the 75th percentile dose. Although the exact reason could not be determined, this may be attributable to a number of factors including deliberate or inadvertent higher dose settings, difference in C-arm position, calibration error, etc. Operative time was 62 mins [IQR 53-74] and EBL was low (25ml [IQR 25-25]. There were no wrong level surgeries, or any intra or post-operative complications. Median post-operative length of stay was 6hrs [IQR 4.4-20.9], with a majority (66.7%) of patients being discharged on the day of surgery. CONCLUSIONS The results of our study suggest that the use of intraoperative navigation using a skin-anchored tracker for posterior cervical laminoforaminotomy is a feasible, safe and accurate technique, resulting in short operative times and minimal complications. Further, it results in negligible radiation exposure to the OR team and low radiation exposure to the patient. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Analysis of Scattering Rays and Shielding Efficiency through Lead Shielding for 0.511 MeV Gamma Rays Based on Skin Dose

Analysis of Scattering Rays and Shielding Efficiency through Lead Shielding for 0.511 MeV Gamma Rays Based on Skin Dose

Abstract 2258: CD73 targeting therapy enhances the anti-tumor effect of radiation therapy in rectal cancer

Abstract [Background and Purpose]Extracellular adenosine exerts strong immunosuppressive activity and is considered as an important metabolic immune-checkpoint molecule. CD73 (ecto-5'-nucleotidase) is the rate-limiting enzyme to produce adenosine, and high CD73 expression in tumor tissue is linked to poor prognosis. However, the role of CD73/adenosine signaling in the response against radiation therapy (RT) is less understood. Here, we examined the anti-tumor effects of the combination of CD73 blockade and RT. [Method]LuM1, a highly metastatic subtype of colon26 (murine colon cancer cell) were subcutaneously (sc) inoculated in Balb/c mouse. At day 12,14 and16, 4Gy RT was locally applied selectively to sc tumor with lead shielding of other body. Blocking CD73 mAb (200μg/body) was intraperitoneally administrated at day 12,14,16,19,22 and 25. The mice were sacrificed at day 28 and the growth of irradiated tumor and non-irradiated lung metastasis was evaluated. For evaluating immune function, tumor and spleen were excised at day 18. In addition, expression of CD73 in 64 human rectal cancer after chemoradiotherapy (CRT) was examined with immunohistochemistry and evaluated for the impact on patient outcome. [Result]Flowcytometric analysis showed that LuM1 positively expressed CD73 which was significantly enhanced by 10Gy RT in vitro. Local RT (4Gy x 2) also enhanced the expression of CD73 in LuM1 of sc tumor (MFI: Median=177, 120-234 vs 65.5, 24.3-72.3, n= 5, p=0.0079). Local RT caused significant delay in growth of sc tumor. However, the addition of anti-CD73 mAb further reduced the tumor weight as compared with isotype control (Μ=0.15g, 0.004-0.29g vs 0.34g, 0.1-0.73g, n=8, p=0.0379). Interestingly, the number of metastases in non-irradiated lung was also significantly decreased by anti-CD73mAb (Μ=1, 0-30 vs 12, 1-70, n=8, p=0.040).The percentage of IFNγ (+)/CD4 (+) cells and IFNγ (+)/CD8a (+) cells of splenocytes were increased in RT +Anti-CD73 groups compared to RT +Anti-Isotype group. (Μ=9.95%, 7.71-16.6% vs 3.64%, 1.01-11.7%, n=6, p=0.0022 and Μ=15.5%, 11.9-24.1% vs 5.98%, 1.51-16.6%, n=6, p=0.041).In addition, the percentage of IFNγ (+)/CD4 (+) cells of tumor infiltrating lymphocytes was increased in RT +Anti-CD73 groups compared to RT +Anti-Isotype group. (Μ=12.2%, 9.77-18.2% vs 7.09%, 1.55-9.41%, n=6, p=0.0022).Among the patients who received CRT, 13 patients with high expression level of CD73 both in remnant tumor cells and stroma showed significantly worse recurrence free survival and overall survival than other 51 patients (p=0.0059 and p=0.0077). [Conclusion]RT enhances the tissue expression of CD73, which can provide large amounts of adenosine in irradiated tumor tissue and may seriously suppress the local immune response and impair the response against RT. Our results suggest that functional blockade of CD73 can enhance not only direct but also abscopal effects of RT possibly through T cell activations, which may improve the outcome of the patients with advanced rectal cancer. Citation Format: Hidenori Tsukui, Hisanaga Horie, Akira Saito, Koji Koinuma, Hideyuki Ohsawa, Hironori Yamaguchi, Yasunaru Sakuma, Yoshinori Hosoya, Kotaro Yoshimura, Alan Lefor, Naohiro Sata, Joji Kitayama. CD73 targeting therapy enhances the anti-tumor effect of radiation therapy in rectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2258.