Leaders in Research & Scientific Sessions

There are a number of perennial destinations for the molecular imaging set that deliver cutting-edge research and promote clinical discussion, but, for many clinicians and researchers, the Society of Nuclear Medicine and Molecular Imaging’s Annual Meeting is the one conference they attend all year. Molecular Imaging Insight was on scene at this year’s meeting held in St. Louis from June 7-11. The following is a selection of some of the most noteworthy scientific sessions.

Depressed elderly may progress more rapidly to Alzheimer’s

The combination of late-life depression and beta-amyloid deposition may lead to a quickening of neurodegeneration and progressive Alzheimer’s disease. Previous research has shown that depression can have an adverse effect on brain anatomy and function, but for this retrospective study, researchers including Axel Rominger, MD, from the department of nuclear medicine at the University of Munich in Germany, compiled international data from a worldwide dementia imaging database and found a clear association between depression in the later stages of life and faster progression of Alzheimer’s.

Rominger says it is quite clear that patients with mild cognitive impairment presenting depressive symptoms have higher beta-amyloid levels in the brain than those who do not, according to recent neuroimaging.

The research included data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database regarding 371 patients with mild cognitive impairment spanning 55 medical institutions. All subjects had been imaged with F-18 florbetapir PET and MRI. Scans clearly revealed that patients with both mild cognitive impairment and depressive symptoms had increased amyloid deposition compared to controls—and significant tracer uptake included the frontal cortex and the anterior as well as posterior cingulate gyrus, which are both implicated in depression.

“Therapeutic options for Alzheimer’s disease are still limited and, therefore, the identification and understanding of contributing risk factors that influence the disease are crucial in ongoing research as they offer the possibilities for future medical intervention,” says co-authoring researcher Matthias Brendel.

Further research is needed to get a better understanding of what this link means in terms of causality and patient management.

Novel HER3 biomarker for advanced breast cancer could lead to new therapies

Human epidermal growth factor receptor 2 (HER2) biomarkers have been the standard for imaging agents that target hormonally active breast cancers that tend to be very aggressive. Now researchers have developed an alternative and potentially more comprehensive biomarker of disease, HER3.

HER2-positive receptor expression is a telltale sign of advanced cancer. An investigative antibody-based agent called Cu-64 DOTA-HER3 F(ab’)2 hits on HER3, a signaler for a HER2-positive tumors across a number of preclinical models using PET. HER3 may hint toward more resistant and aggressive forms of breast cancer, which could translate into a more ideal target for not just imaging, but future treatments.

“If clinically translated, imaging agents such as our HER3 PET Probe represent a maturation of molecular imaging to be able to prospectively guide therapeutic choices for cancer, rather than reporting retrospectively on success or failure of a given therapy,” says principal author Eric P. Wehrenberg-Klee, MD, from Massachusetts General Hospital in Boston. “We hope for clinical translation of this probe over the next 1 to 2 years.”

Stem-cell treatment could halt damage from a heart attack

Acute myocardial infarction causes thousands of fatalities each year. What if there was a way to use stem-cell regeneration to prevent the devastating after-effects of a heart attack? This therapy exists and could potentially prevent dangerous cardiac tissue damage.

The treatment involves the administration of a protein called granulocyte colony stimulating factor (G-CSF), which acts upon bone marrow stem cells that naturally protect heart attack patients from suffering excessive, long-term tissue destruction and reduced cardiac function. The results of the study showed that benefits of G-CSF only increased the more quickly treatment was given after an attack—especially earlier than 37 hours afterward. The improvement was clearly seen by SPECT scan.

Toyama explains: “In our study, we started the intravenous drip infusion of G-CSF during primary [cardiac intervention] just after hospitalization. It’s novel. We used I-123 BMIPP imaging for fatty acid metabolism and Tc-99m MIBI imaging for myocardial perfusion and cardiac function. Those parameters were very beneficial to find the improvement after G-CSF treatment.”

For this study, researchers imaged a total of 40 patients who were administered either treatment with G-CSF or saline control starting at the time of cardiac intervention and continuing for a total of five days. A year of follow up stress SPECT gauged the effects of treatment, including rates of revascularization and restenosis and further cardiac events. Findings of the study revealed that earlier initiation of G-CSF therapy after acute myocardial infarction improves cardiac function, fatty acid metabolism and blood flow.

If further study validates these data, a stem-cell therapy for victims of heart attack could be on the horizon. “This research will be available for patients [of acute heart attack] in the future after a multicenter trial with a large number of patients is performed,” notes Toyama.

Circulating cancer cells count down to metastasis

High-powered radioluminescence microscopy can home in on extremely scarce malignant cells among billions of normal cells in just 7.5 milliliters of blood. Leveraging the molecular imaging of circulating tumor cells (CTCs) could mean early detection of metastasis and the potential to improve survival for patients with several varieties of cancer.

SNMMI projects that metastasis accounts for about 90 percent of cancer deaths. Apparently CTC have been the subject of research since the late 1890s, but no one has been able to apply it to translational medicine. The technique presented by this study combines not only radioluminescence microscopy, which combines nuclear medicine and optical imaging, but also single-cell autoradiography (SCAR). This methodology is applied for localization of radioactivity micro-distribution in individual cells for the imaging of specific functions. Examples include enzymatic cellular metabolism or selected receptor expression.

“Researchers have shown that CTC can be shed from the patient’s primary tumor or from the patient’s metastases. Therefore, CTCs might be the biomarkers that are the most representative of a patient’s disease as a whole,” asserts Laura S. Sasportas, a PhD candidate in the Gambhir Lab in the department of bioengineering at Stanford University in Stanford, Calif. “They could be ideal candidates for a real-time ‘liquid biopsy’ of the tumor,” she says. “The characterization of the properties of CTCs is poised to offer valuable information for predicting and monitoring a patient’s response to therapy.”

In recent years, researchers have begun to piece apart CTCs at the genomic, RNA transcriptomic and proteomic space, but this may be the first time that the focus is on the metabolomics of CTCs.

In a sample of blood from a breast cancer patient, there may be just a few hundred cancer cells. For this study, researchers isolated blood from preclinical models of breast cancer and imaged them using radioluminescence microscopy and SCAR with F-18 FDG. Results showed that fewer than 3 percent of CTCs indicated increased cellular metabolism when compared to the original cell line. It is still not known exactly if this is a biomarker for metastasis, aggressiveness of disease and chance of survival.

“Several clinical studies [conducted with the FDA-approved CellSearch CTC detection system] have shown that the number of CTCs detected in a patient’s blood sample is correlated with the patient’s chances of survival,” adds Sasportas. “This demonstrates the utility of counting CTCs as a prognosis biomarker for many types of cancer.”

Nethertheless, still more research in larger clinical trials are needed to strengthen the theory.

PSMA-PET/CT: New radiotracer pictures more prostate tumors

Few options remain for patients with chemical-castration resistant prostate cancer and even effective imaging can be tough once advanced metastases take hold. However, an emerging radiotracer narrows in on prostate-specific anatomy and finds elusive lesions. The tracer is F-18 DCFBC, a small-molecule PET agent among a group of agents that bind to prostate-specific membrane antigen (PSMA).

PSMA is present even in healthy cells, but in malignant cells an increased uptake of radiotracer can indicate disease. This research looks particularly at the efficacy of the radiotracer when used with PET/CT for the imaging of both castration-sensitive and resistant prostate cancer.

“F-18 DCFBC is one of several emerging small molecule PET radiopharmaceuticals for prostate cancer that promise to bring functional imaging for prostate cancer into clinical reality in the near future,” says Steve Cho, MD, assistant professor of nuclear medicine and PET in the department of radiology at Johns Hopkins University School of Medicine in Baltimore. “F-18 DCFBC and other emerging PSMA and prostate cancer imaging agents will help greatly improve patient management and our understanding of prostate cancer beyond what is currently known.”

The research included imaging of 12 patients in an ongoing clinical trial. Seven of the prostate cancer patients had higher PSMA levels, which, with increased folate levels, were positively associated with castration-resistant status. F-18 DCFBC performed comparably to conventional imaging except in highly scarred bone metastases and was actually superior to the standard for the cervical spine or where there were signs of degeneration, and in lymph nodes that were smaller than a centimeter.

“PSMA-based functional imaging such as F-18 DCFBC PET promises to help patients with prostate cancer by the following: improving detection of both primary and metastatic prostate cancer and therapy response assessment and improving therapy development,” explains Cho. “Patients will be able to start treatment or switch to an appropriate treatment regimen by using functional imaging, in conjunction with other non-imaging biomarkers, to greatly improve their clinical management and quality of life while minimizing adverse effects.” 

This radiotracer is still under investigation and researchers are currently looking into standardizing radiochemistry and biodistribution in multicenter clinical trials.

Molecular Imaging Insight will continue its SNMMI conference coverage with the Mid-Winter Meeting from January 22-25, in San Antonio, Texas. Some of the topics on the agenda are hybridSPECT and PET, particularly the potential of PET/MR; the role of amyloid imaging; and the development of targeted radionuclide cancer therapy, as well as innovations in cardiovascular imaging, and quantitative molecular imaging in research practices.