Life Sciences
Preclinical Studies

Preclinical studies

SARRP was created to mimic clinical treatments.  It has an onboard CBCT to use for targeted planning where the system can deliver a beam as small as 0.5mm. Pre-clinically the machine can be used for replicating current treatments, evaluating possible new treatments, radiation damage and evaluation of the histology and biology of the specific target.  

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Cancer Studies by Site

Radiotherapy for cancer can be given as curative or palliative treatment. Research focuses on curative treatments with radiation alone or in combination with other treatments. Also studied are the side effects radiation can cause.

 

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Head and Neck:

These researchers attempted to use SARRP to mimic a clinical treatment. They used a head and neck human tumor in a nude mouse model. They imaged these mice on a PET and created a plan based on the area of interest and a boost to the area of high FDG uptake. This PET image was fused with SARRP CT image while the mouse was anesthetized. 10Gy was given using a 15mm collimator to the whole tumor. The boost was treated with 10Gy using a non-coplanar dynamic arc with the 5mm collimator. The researchers found that a PET/CT with the SARRP can allow for pre-clinical validation of PET image-guided dose escalation IMRT treatments.

 

Bone:

A study of the effects of radiation on a specific part of the bone. Mesenchymal stem cells survival was affected the addition of free radicals created during irradiation of the bone
GI tract:

In contrast to popular belief, there is not one central necrotic area but several very small repeating areas of hypoxia.

 

Pancreas:

This is a combination radiation plus radiosensitizer study in prostate cancer cell lines. AUY922, a Hsp90 inhibitor, caused radiosensitization in both prostate cancer cell lines used. Radiation Therapy plus AUY922 produced tumor growth delay compared to radiation alone or AUY922 alone.

 

Prostate:

These researchers created Gold-Loaded brachytherapy spacers (GBS). These were implanted in prostate mice models and evaluated with SARRP CBCT over time to evaluate the release of the GBS diffusion. The burst and diffusion was also simulated by injecting into the tumor volume a solution of 20 mg Au/mL concentration into 20 uL of phosphate buffered saline. CBCTs were taken at 0.5, 48, 120, 144 and 160 hours after diffusion. The pixels were measured by their intensity. The GBS had a CT intensity that decreased 160% over the time period. The Au solution decreased in CT intensity by 140%. The researchers conclude that these two methods offer a lasting volume in the prostate which could allow for boost treatments and salvage brachytherapy.

 

Lung:

Proteasome inhibitors were studied as a radiosensitizer with radiation in NSCLC tumors. They found decreases in the homologous recombination after proteasome inhibitors plus radiation causing double strand DNA breaks. They were also found to block the KF-κB pathway by interfering with degredation of IκBα. This rescued the bortezomib-induced radiosensitivity. Alternatively radiosensitivity could be caused by the induction of apoptosis. Many studies have shown an increase in apoptosis after bortezomib treatment. Reduced growth was seen in xenografts after a combination therapy of proteasome inhibitors and RT.

 

Cranial:

In this study, Pulsed low dose rate irradiation is defined as 0.2Gy delivered 10 times separated by 3 minutes for each irradiation to complete a fraction. This was compared to Stereotactic Radiotherapy in 2Gy fractions. Both types of irradiation were given in 10 fractions. It was found that PLDR offered better tumor control and lower normal tissue sparing most likely due to preservation of the vascular density.

 

Research Platform

To find out more about the SARRP Platform and to understand how the system can be utilised for studying the above sites contact our technical team here.

Non-Cancerous Diseases

Radiotherapy can be used to treat benign diseases or to induce bone marrow suppression for transplants. In research, radiation can also be used to induce injury to study the effects, doses and treatments.

 

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Hedgehog pathway has been implicated in tumor recurrence. Inhibitors of this pathway have shown radioresistance (hepatocellular) and radiosensitivity (esophageal) in vitro. This study on non-small cell lung cancer showed no significant radioresistance in vitro. In vivo (xenograft and orthotopic models) both showed great radiosensitivity verified by CBCT on SARRP.

 

Research Platform

To find out more about the SARRP Platform and to understand how the system can be utilised for studying non-cancerous diseases contact our technical team here.

Gold Nanoparticles

Some therapy applications allow the tumor to be more susceptible to radiation called radiosensitizers. In cases where radiation is a common course of treatment but not very effective, radiosensitizers can increase the benefit from this treatment in a great way.
Gold Nanoparticles are great tools in radiotherapy. They can be used to sensitize tissues to radiation, tumor detection and meditate drug delivery.

 

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These researchers created Gold-Loaded brachytherapy spacers (GBS). These were implanted in prostate mice models and evaluated with SARRP CBCT over time to evaluate the release of the GBS diffusion. The burst and diffusion was also simulated by injecting into the tumor volume a solution of 20 mg Au/mL concentration into 20 uL of phosphate buffered saline. CBCTs were taken at 0.5, 48, 120, 144 and 160 hours after diffusion. The pixels were measured by their intensity. The GBS had a CT intensity that decreased 160% over the time period. The Au solution decreased in CT intensity by 140%. The researchers conclude that these two methods offer a lasting volume in the prostate which could allow for boost treatments and salvage brachytherapy.

 

Research Platform

The SARRP Platform allows for imaging and irradiation with gold nanoparticles allowing researchers to study each of these methods. To find out more about the SARRP Platform click here.

Immunology

Immunology is making a big impact in the Radiation Oncology world as a combination therapy. With the different tumor mechanisms, these multi-modality approaches may offer curative outcomes in preclinical studies.

 

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Transforming growth factor-β (TGFβ) has pro-tumorigenic activities and immunosuppressive qualities. Currently there are TGFβ inhibitors in clinical trials. Radiation Therapy induces TGFβ activity which elicits immunogenic signals but creates immunosuppressive effects in the tumor microenvironment.

This group of researchers tested the inhibition of TGFβ in a breast cancer model with radiation. The mice were injected with TGFβ neutralizing antibody 1D11 on day 13 after implantation. They were irradiated 24 hours later with 5 fractions of 6Gy each. The TGFβ neutralizing antibody had no effect on the turmo growth. Radiation therapy plus TGFβ inhibition showed significant tumor regression compared to Radiation therapy alone. There was a large reduction in tumor-associated macrophages (CD11b+Gr1+/intF4/80+). They found that IL12 was upregulated and IL10 and CXCL1 were decreased.

The researchers concluded that TGFβ inhibitors sensitize tumor cells to radiation therapy and create a tumor microenvironment that promotes tumor control. TGFβ blockade sensitizes tumor cells to RT and generates a tumor microenvironment that promotes tumor control. TGFβ inhibition also alleviates tumor suppressive consequences of radiation and creates a pro-immunogenic signal. Together, these actions can achieve persistent tumor control.

 

Research Platform

The SARRP can be used to visualize targets, localize and treat them. Researchers can show how immunotherapy agents plus radiation in a specific area can enhance a treatment protocol.. To find out more about the SARRP Platform click here.