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The treatment of cancer using targeted radionuclide therapy is of interest to nuclear medicine and radiation oncology because of its potential for killing tumor cells while minimizing dose-limiting toxicities to normal tissue. The ionizing radiations emitted by radiopharmaceuticals deliver radiation absorbed doses over protracted periods of time with continuously varying dose rates. As targeted radionuclide therapy becomes a more prominent part of cancer therapy, accurate models for estimating the biologically effective dose (BED) or equieffective dose (EQD2α/β) will become essential for treatment planning. This study examines the radiobiological impact of the dose rate increase half-time during the uptake phase of the radiopharmaceutical. MDA-MB-231 human breast cancer cells and V79 Chinese hamster lung fibroblasts were irradiated chronically with 662 keV γ rays delivered with time-varying dose rates that are clinically relevant. The temporal dose-rate patterns were: 1. acute, 2. exponential decrease with a half-time of 64 h (Td = 64 h), 3. initial exponential increase to a maximum (half time Ti = 2, 8 or 24 h) followed by exponential decrease (Td = 64 h). Cell survival assays were conducted and surviving fractions were determined. There was a marked reduction in biological effect when Ti was increased. Cell survival data were tested against existing dose-response models to assess their capacity to predict response. Currently accepted models that are used in radiation oncology overestimated BED and EQD2α/β at low-dose rates and underestimated them at high-dose rates. This appears to be caused by an adaptive response arising as a consequence of the initial low-dose-rate phase of exposure. An adaptive response function was derived that yields more accurate BED and EQD2α/β values over the spectrum of dose rates and absorbed doses delivered. Our experimental data demonstrate a marked increase in cell survival when the dose-rate-increase half-time is increased, thereby suggesting an adaptive response arising as a consequence of this phase of exposure. We have modified conventional radiobiological models used in the clinic for brachytherapy and external beams of radiation to account for this phenomenon and facilitate their use for treatment planning in targeted radionuclide therapy.

Background: Digital media is an effective tool to enhance brand recognition and is currently referenced by more than 40% of orthopedic patients when selecting a physician. The purpose of this study was to evaluate the use of social media among foot and ankle (F&A) orthopedic surgeons, and the impact of that social media presence on scores of a physician-rated website (PRW). Methods: Randomly selected F&A orthopedic surgeons from all major geographical locations across the United States were identified using the AAOS.org website. Internet searches were then performed using the physician’s name and the respective social media platform. A comprehensive social media use index (SMI) was created for each surgeon using a scoring system based on social media platform use. The use of individual platforms and SMI was compared to the F&A surgeon’s Healthgrades scores. Descriptive statistics, unpaired Student t tests, and linear regression were used to assess the effect of social media on the PRW scores. Results: A total of 123 board-certified F&A orthopedic surgeons were included in our study demonstrating varying social media use: Facebook (48.8%), Twitter (15.4%), YouTube (23.6%), LinkedIn (47.9%), personal website (24.4%), group website (52.9%), and Instagram (0%). The mean SMI was 2.4 ± 1.6 (range 0-7). Surgeons who used a Facebook page were older, whereas those using a group website were younger ( P < .05). F&A orthopedic surgeons with a YouTube page had statistically higher Healthgrades scores compared to those without ( P < .05). Conclusion: F&A orthopedic surgeons underused social media platforms in their clinical practice. Among all the platforms studied, a YouTube page was the most impactful social media platform on Healthgrades scores for F&A orthopedic surgeons. Given these findings, we recommend that physicians closely monitor their digital identity and maintain a diverse social media presence including a YouTube page to promote their clinical practice. Level of Evidence: Level IV.

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The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy are generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Methods Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. Results The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/hr and a minimum dose rate of 0.01 cGy/hr. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/hr. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. Conclusion The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides.

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Nonuniform dose distributions among disseminated tumor cells can be a significant limiting factor in targeted α therapy. This study examines how cocktails of radiolabeled antibodies can be formulated to overcome this limitation. Methods: Cultured MDA-MB-231 human breast cancer cells were treated with different concentrations of a cocktail of 4 fluorochrome-conjugated monoclonal antibodies. The amount of each antibody bound to each cell was quantified using flow cytometry. A spreadsheet was developed to "arm" the antibodies with any desired radionuclide and specific activity, calculate the absorbed dose to each cell, and perform a Monte Carlo simulation of the surviving fraction of cells after exposure to cocktails of different antibody combinations. Simulations were performed for the α-particle emitters 211 At, 213 Bi, and 225 Ac. Results: Activity delivered to the least labeled cell can be increased by 200%-400% with antibody cocktails, relative to the best-performing single antibody. Specific activity determined whether a cocktail or a single antibody achieved greater cell killing. With certain specific activities, cocktails outperformed single antibodies by a factor of up to 244. There was a profound difference (#16 logs) in the surviving fraction when a uniform antibody distribution was assumed and compared with the experimentally observed nonuniform distribution. Conclusion: These findings suggest that targeted α therapy can be improved with customized radiolabeled antibody cocktails. Depending on the antibody combination and specific activity of the radiolabeled antibodies, cocktails can provide a substantial advantage in tumor cell killing. The methodology used in this analysis provides a foundation for pretreatment prediction of tumor cell survival in the context of personalized cancer therapy.

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