Interim Scan during Prostate Cancer Therapy Helps Guide Treatment

New prostate cancer research shows that adding an interim scan during therapy can help guide a patient’s treatment. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging of patients with metastatic castration-resistant prostate cancer after two cycles of lutetium-177 (177Lu)-PSMA radioligand therapy has shown a significant predictive value for patient survival. The research was presented at the 2019 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI).

According to the National Cancer Institute, currently the five-year survival rate for men with metastatic prostate cancer is 30.5 percent. Early assessment of treatment effectiveness is essential to providing optimal care.

In phase 2 trials, 177Lu-PSMA therapy has shown promising results in treating patients with metastatic castration-resistant prostate cancer. The therapy typically involves a preliminary PSMA PET scan to identify patients who are eligible for the treatment. While interim PET scans have shown high predictive value for lymphoma patients, this concept has not been previously explored in prostate cancer patients undergoing 177Lu-PSMA therapy.

The retrospective analysis was conducted at Klinikum rechts der Isar hospital, Technical University Munich, Germany including patients who underwent gallium-68 (68Ga)-PSMA11 PET/CT at baseline and after two cycles of 177Lu-PSMA RLT under a compassionate use program.

Instead of standardized uptake value, which is the parameter generally used in such analyses, researchers used qPSMA, an in-house developed software, to evaluate the whole-body tumor burden. “Tumor response was assessed by the changes in PSMA-avid tumor volume from baseline to the second PSMA PET using three classification methods,” explained Andrei Gafita, MD. “Subsequently, we found that tumor response assessed on interim PSMA PET after two RLT cycles was associated with overall survival.”

Gafita stated, “Our results therefore show that interim PSMA PET can be used for therapeutic response assessment in patients undergoing 177Lu-PSMA RLT. Furthermore, occurrence of new lesions in PSMA PET is a prognostic factor for disease progression and could be included in defining tumor response based on PSMA PET imaging.”

“While further analyses involving clinical parameters are warranted,” Gafita adds, “this analysis paves the way for use of interim PSMA PET in a prospective setting during 177Lu-PSMA radioligand therapy.”

Source: Society of Nuclear Medicine and Molecular Imaging


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New Radiotracer Can Identify Nearly 30 Types of Cancer

A novel class of radiopharmaceuticals has proven effective in non-invasively identifying nearly 30 types of malignant tumors, according to research published in the June issue of The Journal of Nuclear Medicine. Using 68Ga-FAPI positron emission tomography/computed tomography (PET/CT), researchers were able to image a wide variety of tumors with very high uptake and image contrast, paving the way for new applications in tumor characterization, staging and therapy.

The 68Ga-FAPI radiotracer targets cancer-associated fibroblasts, which can contribute up to 90 percent of a tumor’s mass. Many cancer-associated fibroblasts differ from normal fibroblasts by their specific expression of the fibroblast activation protein, or FAP. FAP-specific inhibitors were first developed as conventional anticancer drugs; now they have been advanced into tumor-targeting radiopharmaceuticals.

In the retrospective study, researchers used PET/CT to image 80 patients with 28 different kinds of cancer, aiming to quantify 68Ga-FAPI uptake in primary, metastatic or recurring cancers. All patients were referred for experimental diagnostics by their treating oncologists because they were facing an unmet diagnostic challenge that could not be solved sufficiently with standard methods. The injected activity for the 68Ga-FAPI examinations was 122-312 MBq, and the PET scans were initiated one hour after injection. Tumor tracer uptake was measured by SUVmean and SUVmax.

All patients tolerated the examination well. As the overall SUV mean, median and range of 68Ga-FAPI in primary tumors and metastatic lesions did not differ significantly, researchers analyzed all results in one group.

The highest average SUVmax (SUVmax >12) was found in sarcoma, esophageal, breast, cholangiocarcinoma and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax <6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic and gastric cancers. The average SUVmax of hepatocellular, colorectal, head-neck, ovarian, pancreatic and prostate cancer was intermediate (SUVmax 6-12). In addition, the tumor-to-background ratios were more than three-fold in the intermediate group and more than six-fold in the high-intensity uptake group, resulting in high image contrast and excellent tumor delineation.

“The remarkably high uptake of 68Ga-FAPI makes it useful for many cancer types, especially in cases where traditional 18F-FDG PET/CT faces limitations,” said Uwe Haberkorn, MD, professor of nuclear medicine at the University Hospital of Heidelberg and the German Cancer Research Center in Heidelberg, Germany. “For example, low-grade sarcomas generally have a low uptake of 18F-FDG, causing an overlap between benign and malignant lesions. In breast cancer, 18F-FDG PET/CT is commonly used in recurrence, but not generally recommended for initial staging. And for esophageal cancer, 18F-FDG PET/CT often has only a low to moderate sensitivity for lymph node staging.”

In contrast to 18F-FDG PET/CT, 68Ga-FAPI PET/CT can be performed without specific patient preparation such as fasting or recline during uptake time. This is a potential operational advantage for 68Ga-FAPI PET/CT, as it stands to improve patient comfort and accelerate work-flow.

According to Haberkorn, 68Ga-FAPI offers the possibility of a theranostic approach in the future. “Cancer associated fibroblasts have been described as immunosuppressive and as conferring resistance to chemotherapy, which makes them attractive targets for combination therapies,” he said. “Because the 68Ga-FAPI tracers contain the universal DOTA-chelator, it is possible to label them with therapeutic radionuclides whose half-life fits to the tumor retention time of the carrier molecule. Since the tracer has been observed to accumulate in several important tumor entities, there may be a huge field of therapeutic application to be evaluated in the future.”

Source: Society of Nuclear Medicine and Molecular Imaging


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Human Images from the World’s First Total-body Medical Scanner Unveiled

EXPLORER, the world’s first medical imaging scanner that can capture a 3-D picture of the whole human body at once, has produced its first scans.

The brainchild of UC Davis scientists Simon Cherry and Ramsey Badawi, EXPLORER is a combined positron emission tomography (PET) and x-ray computed tomography (CT) scanner that can image the entire body at the same time. Because the machine captures radiation far more efficiently than other scanners, EXPLORER can produce an image in as little as one second and, over time, produce movies that can track specially tagged drugs as they move around the entire body.

The developers expect the technology will have countless applications, from improving diagnostics to tracking disease progression to researching new drug therapies.

The first images from scans of humans using the new device will be shown at the upcoming Radiological Society of North America meeting, which starts on Nov. 24th in Chicago. The scanner has been developed in partnership with Shanghai-based United Imaging Healthcare (UIH), which built the system based on its latest technology platform and will eventually manufacture the devices for the broader healthcare market.

“While I had imagined what the images would look like for years, nothing prepared me for the incredible detail we could see on that first scan,” said Cherry, distinguished professor in the UC Davis Department of Biomedical Engineering. “While there is still a lot of careful analysis to do, I think we already know that EXPLORER is delivering roughly what we had promised.

Badawi, chief of Nuclear Medicine at UC Davis Health and vice-chair for research in the Department of Radiology, said he was dumbfounded when he saw the first images, which were acquired in collaboration with UIH and the Department of Nuclear Medicine at the Zhongshan Hospital in Shanghai.

“The level of detail was astonishing, especially once we got the reconstruction method a bit more optimized,” he said. “We could see features that you just don’t see on regular PET scans. And the dynamic sequence showing the radiotracer moving around the body in three dimensions over time was, frankly, mind-blowing. There is no other device that can obtain data like this in humans, so this is truly novel.”

Badawi and Cherry first conceptualized a total-body scanner 13 years ago. Their idea was kick-started in 2011 with a $1.5 million grant from the National Cancer Institute, which allowed them to establish a wide-ranging consortium of researchers and other collaborators. And it got a giant boost in 2015 with a $15.5 million grant from the NIH. The funding allowed them to team up with a commercial partner and get the first EXPLORER scanner built.

Cherry said he expects EXPLORER will have a profound impact on clinical research and patient care because it produces higher-quality diagnostic PET scans than have ever been possible. EXPLORER also scans up to 40 times faster than current PET scans and can produce a diagnostic scan of the whole body in as little as 20-30 seconds.

Alternatively, EXPLORER can scan with a radiation dose up to 40 times less than a current PET scan, opening new avenues of research and making it feasible to conduct many repeated studies in an individual, or dramatically reduce the dose in pediatric studies, where controlling cumulative radiation dose is particularly important.

“The tradeoff between image quality, acquisition time and injected radiation dose will vary for different applications, but in all cases, we can scan better, faster or with less radiation dose, or some combination of these,” Cherry said.

For the first time, an imaging scanner will be able to evaluate what is happening in all the organs and tissues of the body simultaneously. For example, it could quantitatively measure blood flow or how the body takes up glucose everywhere in the body. Researchers envision using the scanner to study cancer that has spread beyond a single tumor site, inflammation, infection, immunological or metabolic disorders and many other diseases.

UC Davis is working closely with UIH to get the first system delivered and installed at the EXPLORER Imaging Center in leased space in Sacramento, and the researchers hope to begin research projects and imaging patients using EXPLORER as early as June 2019. The UC Davis team also is working closely with Hongcheng Shi, director of Nuclear Medicine at Zhongshan Hospital in Shanghai to continue and expand the scope of early human studies on the scanner.

“I don’t think it will be long before we see at a number of EXPLORER systems around the world,” Cherry said. “But that depends on demonstrating the benefits of the system, both clinically and for research. Now, our focus turns to planning the studies that will demonstrate how EXPLORER will benefit our patients and contribute to our knowledge of the whole human body in health and disease.”

Source : UC Davis

3D Images of Cancer Cells in the Body

Medical physicists at Martin Luther University Halle-Wittenberg (MLU) have developed a new method that can generate detailed three-dimensional images of the body’s interior. This can be used to more closely investigate the development of cancer cells in the body. The research group presents its findings in “Communication Physics”, a journal published by the Nature Publishing Group.

Clinicians and scientists are in need of a better understanding of cancer cells and their properties in order to provide targeted cancer treatment. Individual cancer cells are often examined in test tubes before the findings are tested in living organisms. “Our aim is to visualise cancer cells inside the living body to find out how they function, how they spread and how they react to new therapies,” says medical physicist Professor Jan Laufer from MLU. He specialises in the field of photoacoustic imaging, a process that uses ultrasound waves generated by laser beams to produce high-resolution, three-dimensional images of the body’s interior.

“The problem is that tumour cells are transparent. This makes it difficult to use optical methods to examine tumours in the body,” explains Laufer whose research group has developed a new method to solve this problem: First the scientists introduce a specific gene into the genome of the cancer cells. “Once inside the cells, the gene produces a phytochrome protein, which originates from plants and bacteria. There it serves as a light sensor,” Laufer continues. In the next step, the researchers illuminate the tissue with short pulses of light at two different wavelengths using a laser. Inside the body, the light pulses are absorbed and converted into ultrasonic waves. These waves can then be measured outside the organism and two images of the body’s interior can be reconstructed based on this data. “The special feature of phytochrome proteins is that they alter their structure and thus also their absorption properties depending on the wavelength of the laser beams. This results in changes to the amplitude of the ultrasound waves that are generated in the tumour cells. None of the other tissue components, for example blood vessels, have this property – their signal remains constant,” Laufer says. By calculating the difference between the two images, a high-resolution, three-dimensional image of the tumour cells is created, which is free of the otherwise overwhelming background contrast.

The development of Halle’s medical physicists can be applied to a wide range of applications in the preclinical research and the life sciences. In addition to cancer research, the method can be used to observe cellular and genetic processes in living organisms.

Source: Martin-Luther-University

New Instrument Lets Doctors View the Entire Eye with Unprecedented Level of Detail

Researchers have developed the first instrument that can provide a detailed image of the entire eye. By incorporating a lens that changes optical parameters in response to an electric current, the innovative technology can produce higher quality images than currently available and could make eye examinations faster and more comfortable for patients by avoiding the need to undergo imaging with multiple instruments to look at different areas of the eye.

“Diseases such as glaucoma affect both the front and back portions of the eye,” said Ireneusz Grulkowski, whose research team at Nicolaus Copernicus University, Poland, worked with Pablo Artal’s team at the Universidad de Murcia, Spain to develop the new imaging system. “An instrument that can examine the whole eye will improve the patient’s experience because they won’t have to go through imaging with different devices. It might also one day reduce the number of instruments — which can be quite expensive — needed in an ophthalmology clinic.”

In Optica, The Optical Society’s journal for high impact research, the researchers show that their new optical coherence tomography (OCT) imaging system can not only image both the front and the back of the eye, but can also image the interfaces of the eye’s vitreous gel with the retina and lens with unprecedented detail. This new imaging capability could allow scientists to better understand how the vitreous gel that fills the eye interacts with the retina and why it can sometimes become detached with aging.

“We also want to use our instrument to measure opacities in the eye’s crystal lens and the vitreous to better understand how various parts of the eye affect the deterioration of vision,” said Grulkowski. “We believe that the ability to measure these opacities and other properties of the eye that couldn’t be examined before will open up many new ophthalmology applications for OCT.”

Increasing imaging depth

The new system is based on OCT, which is commonly used to acquire very detailed, cross-sectional ophthalmology images. Most clinical instruments are limited to imaging depths of 2 to 3 millimeters, and it is difficult to switch between imaging the front and back portions of the eye because the eye is composed of elements that bend the light to focus it onto the retina.

To overcome these challenges, the researchers used an electrically tunable lens to build an OCT instrument that could focus light in a way that enabled whole-eye imaging. Unlike standard glass or plastic lenses, which have fixed parameters, the optical properties of an electrically tunable lens can be dynamically controlled using an electric current.

The OCT system also incorporated a newly commercialized swept light source — a laser that continuously changes wavelength very rapidly. The wavelength-tunable laser improves the resolution and speed of OCT compared to systems that use other light sources. The researchers integrated high-speed electronics to achieve the imaging depth necessary to enable whole eye imaging.

“We incorporated the electrically tunable lens into a custom-made system that represents the latest generation of OCT technology,” said Grulkowski. “We set out to show that we could image both the front and back of the eye without changing instruments. However, we were also able to show that our instrument enhanced the image quality of the OCT images.”

The researchers used their new system to measure the anatomical characteristics of the eyes of seven healthy people. Measurements calculated using images from the new system correlated well with those obtained with an ocular biometer, the standard clinical device used today.

Next steps

The researchers are now working to optimize the instrument for imaging of the entire vitreous gel, not just where it interfaces with the lens and retina. The vitreous gel has not been studied intensively and is difficult to image because it is highly transparent. The ability to image the entire vitreous could allow OCT to be used to guide procedures that involve the removal of the vitreous gel from the eye, which is sometimes done to repair retinal detachment.

Although the laboratory version of the set-up is ready to use, further steps will be taken to translate the technology to the clinic. The scientists are focused on optimizing the scan areas and developing processing tools for automatic measurement of the dimensions of the eye. These improvements will enable advanced studies of the proposed scan regimes on a group of patients with different types of opacification in the eye.

Source: The Optical Society


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