Role of miR-2392 in driving SARS-CoV-2 infection.

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans.

The Great Deceiver: miR-2392's Hidden Role in Driving SARS-CoV-2 Infection.

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia as well as promoting many symptoms associated with COVID-19 infection. We demonstrate miR-2392 is present in the blood and urine of COVID-19 positive patients, but not detected in COVID-19 negative patients. These findings indicate the potential for developing a novel, minimally invasive, COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we have developed a novel miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters and may potentially inhibit a COVID-19 disease state in humans.

Advanced Small Animal Conformal Radiation Therapy Device.

We have developed a small animal conformal radiation therapy device that provides a degree of geometrical/anatomical targeting comparable to what is achievable in a commercial animal irradiator. small animal conformal radiation therapy device is capable of producing precise and accurate conformal delivery of radiation to target as well as for imaging small animals. The small animal conformal radiation therapy device uses an X-ray tube, a robotic animal position system, and a digital imager. The system is in a steel enclosure with adequate lead shielding following National Council on Radiation Protection and Measurements 49 guidelines and verified with Geiger-Mueller survey meter. The X-ray source is calibrated following AAPM TG-61 specifications and mounted at 101.6 cm from the floor, which is a primary barrier. The X-ray tube is mounted on a custom-made "gantry" and has a special collimating assembly system that allows field size between 0.5 mm and 20 cm at isocenter. Three-dimensional imaging can be performed to aid target localization using the same X-ray source at custom settings and an in-house reconstruction software. The small animal conformal radiation therapy device thus provides an excellent integrated system to promote translational research in radiation oncology in an academic laboratory. The purpose of this article is to review shielding and dosimetric measurement and highlight a few successful studies that have been performed to date with our system. In addition, an example of new data from an in vivo rat model of breast cancer is presented in which spatially fractionated radiation alone and in combination with thermal ablation was applied and the therapeutic benefit examined.

Radiation-induced alterations in mitochondria of the rat heart.

Radiation therapy for the treatment of thoracic cancers may be associated with radiation-induced heart disease (RIHD), especially in long-term cancer survivors. Mechanisms by which radiation causes heart disease are largely unknown. To identify potential long-term contributions of mitochondria in the development of radiation-induced heart disease, we examined the time course of effects of irradiation on cardiac mitochondria. In this study, Sprague-Dawley male rats received image-guided local X irradiation of the heart with a single dose ranging from 3-21 Gy. Two weeks after irradiation, left ventricular mitochondria were isolated to assess the dose-dependency of the mitochondrial permeability transition pore (mPTP) opening in a mitochondrial swelling assay. At time points from 6 h to 9 months after a cardiac dose of 21 Gy, the following analyses were performed: left ventricular Bax and Bcl-2 protein levels; apoptosis; mitochondrial inner membrane potential and mPTP opening; mitochondrial mass and expression of mitophagy mediators Parkin and PTEN induced putative kinase-1 (PINK-1); mitochondrial respiration and protein levels of succinate dehydrogenase A (SDHA); and the 70 kDa subunit of complex II. Local heart irradiation caused a prolonged increase in Bax/Bcl-2 ratio and induced apoptosis between 6 h and 2 weeks. The mitochondrial membrane potential was reduced until 2 weeks, and the calcium-induced mPTP opening was increased from 6 h up to 9 months. An increased mitochondrial mass together with unaltered levels of Parkin suggested that mitophagy did not occur. Lastly, we detected a significant decrease in succinate-driven state 2 respiration in isolated mitochondria from 2 weeks up to 9 months after irradiation, coinciding with reduced mitochondrial levels of succinate dehydrogenase A. Our results suggest that local heart irradiation induces long-term changes in cardiac mitochondrial membrane functions, levels of SDH and state 2 respiration. At any time after exposure to radiation, cardiac mitochondria are more prone to mPTP opening. Future studies will determine whether this makes the heart more susceptible to secondary stressors such as calcium overload or ischemia/reperfusion.

A novel technique for image-guided local heart irradiation in the rat.

In radiotherapy treatment of thoracic, breast and chest wall tumors, the heart may be included (partially or fully) in the radiation field. As a result, patients may develop radiation-induced heart disease (RIHD) several years after exposure to radiation. There are few methods available to prevent or reverse RIHD and the biological mechanisms remain poorly understood. In order to further study the effects of radiation on the heart, we developed a model of local heart irradiation in rats using an image-guided small animal conformal radiation therapy device (SACRTD) developed at our institution. First, Monte Carlo based simulations were used to design an appropriate collimator. EBT-2 films were used to measure relative dosimetry, and the absolute dose rate at the isocenter was measured using the AAPM protocol TG-61. The hearts of adult male Sprague-Dawley rats were irradiated with a total dose of 21 Gy. For this purpose, rats were anesthetized with isoflurane and placed in a custom-made vertical rat holder. Each heart was irradiated with a 3-beam technique (one AP field and 2 lateral fields), with each beam delivering 7 Gy. For each field, the heart was visualized with a digital flat panel X-ray imager and placed at the isocenter of the 1.8 cm diameter beam. In biological analysis of radiation exposure, immunohistochemistry showed γH2Ax foci and nitrotyrosine throughout the irradiated hearts but not in the lungs. Long-term follow-up of animals revealed histopathological manifestations of RIHD, including myocardial degeneration and fibrosis. The results demonstrate that the rat heart irradiation technique using the SACRTD was successful and that surrounding untargeted tissues were spared, making this approach a powerful tool for in vivo radiobiological studies of RIHD. Functional and structural changes in the rat heart after local irradiation are ongoing.

Effects of late administration of pentoxifylline and tocotrienols in an image-guided rat model of localized heart irradiation.

Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation.

Effects of radiation on the epidermal growth factor receptor pathway in the heart.

PURPOSE: Radiation-induced heart disease (RIHD) is a serious side-effect of thoracic radiotherapy. The epidermal growth factor receptor (EGFR) pathway is essential for the function and survival of cardiomyocytes. Hence, agents that target the EGFR pathway are cardiotoxic. Tocotrienols protect from radiation injury, but may also enhance the therapeutic effects of EGFR pathway inhibitors in cancer treatment. This study investigated the effects of local irradiation on the EGFR pathway in the heart and tests whether tocotrienols may modify radiation-induced changes in this pathway. METHODS: Male Sprague-Dawley rats received image-guided localized heart irradiation with 21 Gy. Twenty four hours before irradiation, rats received a single dose of tocotrienol-enriched formulation or vehicle by oral gavage. At time points from 2 h to 9 months after irradiation, left ventricular expression of EGFR pathway mediators was studied. RESULTS: Irradiation caused a decrease in the expression of epidermal growth factor (EGF) and neuregulin-1 (Nrg-1) mRNA from 6 h up to 10 weeks, followed by an upregulation of these ligands and the receptor erythroblastic leukemia viral oncogene homolog (ErbB)4 at 6 months. In addition, the upregulation of Nrg-1 was statistically significant up to 9 months after irradiation. A long-term upregulation of ErbB2 protein did not coincide with changes in transcription or post-translational interaction with the chaperone heat shock protein 90 (HSP90). Pretreatment with tocotrienols prevented radiation-induced changes at 2 weeks. CONCLUSIONS: Local heart irradiation causes long-term changes in the EGFR pathway. Studies have to address how radiation may interact with cardiotoxic effects of EGFR inhibitors.

SonoKnife for ablation of neck tissue: in vivo verification of a computer layered medium model.

PURPOSE: This study aimed to determine which treatment parameters of the SonoKnife device can be used to safely and effectively perform non-invasive thermal ablation of subcutaneous tissue. METHODS: A three-dimensional computational layered medium model was constructed to simulate thermal ablation treatment of the SonoKnife device. The acoustic and thermal fields were calculated with the Fast Object-Oriented C++ Ultrasound-Simulator software and a finite difference code, respectively. Subcutaneous tissue was represented as layers of skin, fat and muscle. The simulations were conducted for ultrasound frequencies of 1 or 3.5 MHz. The thermal dose model was used to predict the size and location of the ablated regions. The computer simulations were verified by using the SonoKnife to perform subcutaneous ablations in the neck area of healthy pigs, in vivo. Triphenyltetrazolium chloride viability stain was used to differentiate viable tissue from ablated regions ex vivo. RESULTS: The simulations for the layered medium model suggest that operating the SonoKnife at frequency of 1 MHz is more effective and safer than 3.5 MHz providing skin cooling is applied prior to ablation. These predictions were in agreement with the results observed in the animal studies. The required sonication time for ablation increased from 50 to 300 s by using 1 MHz. CONCLUSION: Our modelling and animal studies suggest that 1 MHz with pretreatment skin cooling are the optimal settings to operate the SonoKnife to safely and effectively perform subcutaneous thermal ablation of porcine skin. More work is needed to optimise skin cooling and define the optimal sonication time.

Cardiac inflammation after local irradiation is influenced by the kallikrein-kinin system.

Radiotherapy of intrathoracic and chest wall tumors may lead to exposure of the heart to ionizing radiation, resulting in radiation-induced heart diseases (RIHD). The main manifestations of RIHD become apparent many years after treatment and include cardiomyopathy and accelerated atherosclerosis. This study examines the role of the kallikrein-kinin system (KKS) in RIHD by investigating the cardiac radiation response in a kininogen-deficient Brown Norway Katholiek (BN/Ka) rat model. BN/Ka rats and wild-type Brown Norway (BN) rats were exposed to local heart irradiation with a single dose of 18 Gy or 24 Gy and were observed for 3 to 6 months. Examinations included in vivo and ex vivo cardiac function, histopathology, gene and protein expression measurements, and mitochondrial swelling assays. Upon local heart irradiation, changes in in vivo cardiac function were significantly less in BN/Ka rats. For instance, a single dose of 24 Gy caused a 35% increase in fractional shortening in BN rats compared with a 16% increase in BN/Ka rats. BN rats, but not BN/Ka rats, showed a 56% reduction in cardiac numbers of CD2-positive cells, and a 57% increase in CD68-positive cells, together with a 52% increase in phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2). Local heart irradiation had similar effects on histopathology, mitochondrial changes, and left ventricular mRNA levels of NADPH oxidases in the two genotypes. These results suggest that the KKS plays a role in the effects of radiation on cardiac function and recruitment of inflammatory cells. The KKS may have these effects at least in part by altering Erk1/2 signaling.

Microbeam radiation therapy alters vascular architecture and tumor oxygenation and is enhanced by a galectin-1 targeted anti-angiogenic peptide.

In this study, we sought to determine the therapeutic potential of variably sized (50 µm or 500 µm wide, 14 mm tall) parallel microbeam radiation therapy (MRT) alone and in combination with a novel anti-angiogenic peptide, anginex, in mouse mammary carcinomas (4T1)--a moderately hypoxic and radioresistant tumor with propensity to metastasize. The fraction of total tumor volume that was directly irradiated was approximately 25% in each case, but the distance between segments irradiated by the planar microbeams (width of valley dose region) varied by an order of magnitude from 150-1500 µm corresponding to 200 µm and 2000 µm center-to-center inter-microbeam distances, respectively. We found that MRT administered in 50 µm beams at 150 Gy was most effective in delaying tumor growth. Furthermore, tumor growth delay induced by 50 µm beams at 150 Gy was virtually indistinguishable from the 500 µm beams at 150 Gy. Fifty-micrometer beams at the lower peak dose of 75 Gy induced growth delay intermediate between 150 Gy and untreated tumors, while 500 µm beams at 75 Gy were unable to alter tumor growth compared to untreated tumors. However, the addition of anginex treatment increased the relative tumor growth delay after 500 µm beams at 75 Gy most substantially out of the conditions tested. Anginex treatment of animals whose tumors received the 50 µm beams at 150 Gy also led to an improvement in growth delay from that induced by the comparable MRT alone. Immunohistochemical staining for CD31 (endothelial cells) and αSMA (smooth muscle pericyte-associated blood vessels as a measure of vessel normalization) indicated that vessel density was significantly decreased in all irradiated groups and pericyte staining was significantly increased in the irradiated groups on day 14 after irradiation. The addition of anginex treatment further decreased the mean vascular density in all combination treatment groups and further increased the amount of pericyte staining in these tumors. Finally, evidence of tumor hypoxia was found to decrease in tumors analyzed at 1-14 days after MRT in the groups receiving 150 Gy peak dose, but not 75 Gy peak dose. Our results suggest that tumor vascular damage induced by MRT at these potentially clinically acceptable peak entrance doses may provoke vascular normalization and may be exploited to improve tumor control using agents targeting angiogenesis.

Spatially fractionated radiation induces cytotoxicity and changes in gene expression in bystander and radiation adjacent murine carcinoma cells.

Radiation-induced bystander effects have been extensively studied at low doses, since evidence of bystander induced cell killing and other effects on unirradiated cells were found to be predominant at doses up to 0.5 Gy. Therefore, few studies have examined bystander effects induced by exposure to higher doses of radiation, such as spatially fractionated radiation (GRID) treatment. In the present study, we evaluate the ability of GRID treatment to induce changes in GRID adjacent (bystander) regions, in two different murine carcinoma cell lines following exposure to a single irradiation dose of 10 Gy. Murine SCK mammary carcinoma cells and SCCVII squamous carcinoma cells were irradiated using a brass collimator to create a GRID pattern of nine circular fields 12 mm in diameter with a center-to-center distance of 18 mm. Similar to the typical clinical implementation of GRID, this is approximately a 50:50 ratio of direct and bystander exposure. We also performed experiments by irradiating separate cultures and transferring the medium to unirradiated bystander cultures. Clonogenic survival was evaluated in both cell lines to determine the occurrence of radiation-induced bystander effects. For the purpose of our study, we have defined bystander cells as GRID adjacent cells that received approximately 1 Gy scatter dose or unirradiated cells receiving conditioned medium from irradiated cells. We observed significant bystander killing of cells adjacent to the GRID irradiated regions compared to sham treated controls. We also observed bystander killing of SCK and SCCVII cells cultured in conditioned medium obtained from cells irradiated with 10 Gy. Therefore, our results confirm the occurrence of bystander effects following exposure to a high-dose of radiation and suggest that cell-to-cell contact is not required for these effects. In addition, the gene expression profile for DNA damage and cellular stress response signaling in SCCVII cells after GRID exposure was studied. The occurrence of GRID-induced bystander gene expression changes in significant numbers of DNA damage and cellular stress response signaling genes, providing molecular evidence for possible mechanisms of bystander cell killing.

SonoKnife: feasibility of a line-focused ultrasound device for thermal ablation therapy.

PURPOSE: To evaluate the feasibility of line-focused ultrasound for thermal ablation of superficially located tumors. METHODS: A SonoKnife is a cylindrical-section ultrasound transducer designed to radiate from its concave surface. This geometry generates a line-focus or acoustic edge. The motivation for this approach was the noninvasive thermal ablation of advanced head and neck tumors and positive neck nodes in reasonable treatment times. Line-focusing may offer advantages over the common point-focusing of spherically curved radiators such as faster coverage of a target volume by scanning of the acoustic edge. In this paper, The authors report studies using numerical models and phantom and ex vivo experiments using a SonoKnife prototype. RESULTS: Acoustic edges were generated by cylindrical-section single-element ultrasound transducers numerically, and by the prototype experimentally. Numerically, simulations were performed to characterize the acoustic edge for basic design parameters: transducer dimensions, line-focus depth, frequency, and coupling thickness. The dimensions of the acoustic edge as a function of these parameters were determined. In addition, a step-scanning simulation produced a large thermal lesion in a reasonable treatment time. Experimentally, pressure distributions measured in degassed water agreed well with acoustic simulations, and sonication experiments in gel phantoms and ex vivo porcine liver samples produced lesions similar to those predicted with acoustic and thermal models. CONCLUSIONS: Results support the feasibility of noninvasive thermal ablation with a SonoKnife.

Rapid loss of bone mass and strength in mice after abdominal irradiation.

Localized irradiation is a common treatment modality for malignancies in the pelvic-abdominal cavity. We report here on the changes in bone mass and strength in mice 7-14 days after abdominal irradiation. Male C57BL/6 mice of 10-12 weeks of age were given a single-dose (0, 5, 10, 15 or 20 Gy) or fractionated (3 Gy × 2 per day × 7.5 days) X rays to the abdomen and monitored daily for up to 14 days. A decrease in the serum bone formation marker and ex vivo osteoblast differentiation was detected 7 days after a single dose of radiation, with little change in the serum bone resorption marker and ex vivo osteoclast formation. A single dose of radiation elicited a loss of bone mineral density (BMD) within 14 days of irradiation. The BMD loss was up to 4.1% in the whole skeleton, 7.3% in tibia, and 7.7% in the femur. Fractionated abdominal irradiation induced similar extents of BMD loss 10 days after the last fraction: 6.2% in the whole skeleton, 5.1% in tibia, and 13.8% in the femur. The loss of BMD was dependent on radiation dose and was more profound in the trabecula-rich regions of the long bones. Moreover, BMD loss in the total skeleton and the femurs progressed with time. Peak load and stiffness in the mid-shaft tibia from irradiated mice were 11.2-14.2% and 11.5-25.0% lower, respectively, than sham controls tested 7 days after a single-dose abdominal irradiation. Our data demonstrate that abdominal irradiation induces a rapid loss of BMD in the mouse skeleton. These effects are bone type- and region-specific but are independent of radiation fractionation. The radiation-induced abscopal damage to the skeleton is manifested by the deterioration of biomechanical properties of the affected bone.

An alternating focused ultrasound system for thermal therapy studies in small animals.

PURPOSE: To develop an alternating focused ultrasound system (AFUS) for preclinical studies of thermal and acoustic responses of tumors in small animal models. This work was motivated by the need of noninvasively creating relatively small spheroidal thermal lesions in small targets (e.g., a murine tumor) without damaging the surrounding tissues. METHODS: The AFUS consists of two lead zirconate titanate (PZT-4) spherically curved ultrasound transducers with focal zones crossing each other at a 90 degrees angle. The transducers were independently powered following a programed alternating firing scheme. Before the device design and construction, an acoustic and biothermal model was developed to simulate the ultrasound pressure field and the resulting temperature and thermal dose distributions. A shape factor, sphericity, to quantify the roundness of the lesions was calculated based on the 240 equivalent minutes at 43 degrees C thermal dose contours. A prototype of the AFUS was constructed with two identical transducers of an operating frequency of 2.25 MHz, 38 mm in diameter, and F-number equal to 1.33. To evaluate the performance of the AFUS experimentally, a series of heating in polyacrylamide phantoms, ex vivo porcine liver tissues, and in implanted mouse tumors fibrosarcoma (FSaII) in vivo was conducted. In these experimental cases, the sphericity was calculated and compared based on the visible lesion (a marked change in coloration). RESULTS: As shown in the simulations, the lesions induced in polyacrylamide phantoms, ex vivo porcine liver tissues, and in vivo mouse tumors, the sphericities of the lesions yielded by AFUS heating were approximately 50% higher than those of single focused ultrasound heating as long as moderate intensities were used and the duty cycle pulses were distributed equally among the transducers. CONCLUSIONS: The AFUS is a device capable of noninvasively creating spheroidal thermal lesions in small targets such as murine tumors.

Repression of multiple myeloma growth and preservation of bone with combined radiotherapy and anti-angiogenic agent.

The effects of ionizing radiation, with or without the anti-angiogenic agent anginex (Ax), on multiple myeloma growth were tested in a SCID-rab mouse model. Mice carrying human multiple myeloma cell-containing pre-implanted bone grafts were treated weekly with various regimens for 8 weeks. Rapid multiple myeloma growth, assessed by bioluminescence intensity (IVIS), human lambda Ig light chain level in serum (ELISA), and the volume of bone grafts (caliper), was observed in untreated mice. Tumor burden in mice receiving combined therapy was reduced to 59% (by caliper), 43% (by ELISA), and 2% (by IVIS) of baseline values after 8 weeks of treatment. Ax or radiation alone slowed but did not stop tumor growth. Four weeks after the withdrawal of the treatments, tumor burden remained minimal in mice given Ax + radiation but increased noticeably in the other three groups. Multiple myeloma suppression by Ax + radiation was accompanied by a marked decrease in the number and activity of osteoclasts in bone grafts assessed by histology. Bone graft integrity was preserved by Ax + radiation but was lost in the other three groups, as assessed by microCT imaging and radiography. These results suggest that radiotherapy, when primed by anti-angiogenic agents, may be a potent therapy for focal multiple myeloma.

Prevention and mitigation of acute death of mice after abdominal irradiation by the antioxidant N-acetyl-cysteine (NAC).

Gastrointestinal (GI) injury is a major cause of acute death after total-body exposure to large doses of ionizing radiation, but the cellular and molecular explanations for GI death remain dubious. To address this issue, we developed a murine abdominal irradiation model. Mice were irradiated with a single dose of X rays to the abdomen, treated with daily s.c. injection of N-acetyl-l-cysteine (NAC) or vehicle for 7 days starting either 4 h before or 2 h after irradiation, and monitored for up to 30 days. Separately, mice from each group were assayed 6 days after irradiation for bone marrow reactive oxygen species (ROS), ex vivo colony formation of bone marrow stromal cells, and histological changes in the duodenum. Irradiation of the abdomen caused dose-dependent weight loss and mortality. Radiation-induced acute death was preceded not only by a massive loss of duodenal villi but also, surprisingly, abscopal suppression of stromal cells and elevation of ROS in the nonirradiated bone marrow. NAC diminished these radiation-induced changes and improved 10- and 30-day survival rates to >50% compared with <5% in vehicle-treated controls. Our data establish a central role for abscopal stimulation of bone marrow ROS in acute death in mice after abdominal irradiation.

Dosimetric comparison of helical tomotherapy and linac-IMRT treatment plans for head and neck cancer patients.

The rapid development and clinical implementation of external beam radiation treatment technologies continues. The existence of various commercially available technologies for intensity-modulated radiation therapy (IMRT) has stimulated interest in exploring the differential potential advantage one may have compared with another. Two such technologies, Hi-Art Helical Tomotherapy (HT) and conventional medical linear accelerator-based IMRT (LIMRT) have been shown to be particularly suitable for the treatment of head and neck cancers. In this study, 23 patients who were diagnosed with stages 3 or 4 head and neck cancers, without evidence of distance metastatic disease, were treated in our clinic. Treatment plans were developed for all patients simultaneously on the HT planning station and on the Pinnacle treatment planning system for step-and-shoot IMRT. Patients were treated only on the HT unit, with the LIMRT plan serving as a backup in case the HT system might not be available. All plans were approved for clinical use by a physician. The prescription was that patients receive at least 95% of the planning target volume (PTV), which is 66 Gy at 2.2 Gy per fraction. Several dosimetric parameters were computed: PTV dose coverage; PTV volume conformity index; the normalized total dose (NTD), where doses were converted to 2 Gy per fraction to organs at risk (OAR); and PTV dose homogeneity. Both planning systems satisfied our clinic's PTV prescription requirements. The results suggest that HT plans had, in general, slightly better dosimetric characteristics, especially regarding PTV dose homogeneity and normal tissue sparing. However, for both techniques, doses to OAR were well below the currently accepted normal tissue tolerances. Consequently, factors other than the dosimetric parameters studied here may have to be considered when making a choice between IMRT techniques.