ImmunoSPECT imaging shows that the effectiveness of a newly developed radioimmunotherapy for treating a resistant form of kidney cancer could be diminished when used after another anti-cancer therapy.

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Molecular Imaging Informs Kidney Cancer Treatment

Public release date: 11-Jun-2012 [ | E-mail | Share ]

Contact: Susan Martonik smartonik@snm.org 703-652-6773 Society of Nuclear Medicine

Miami Beach, Fla. (June 11, 2012)A method of molecular imaging that pinpoints hormonally active tissues in the body could change the course of treatment for a remarkable number of neuroendocrine cancer patients, say researchers at the Society of Nuclear Medicine's 59th Annual Meeting.

An investigation of a molecular imaging method used to evaluate neuroendocrine patients prior to treatment was found to change management in more than 35 percent of the patients following imaging.

Patients who were previously considered inoperable went on to have surgery, and patients with previously unknown and extensive cancer who were originally slated for surgery were considered inoperable. Ruling out surgery in cases that are unlikely to be treated successfully with resection saves patients from the stress and potential complications of unnecessary surgeries.

"The study shows that this particular molecular imaging technique does significantly change patient management, identifying operable and curable symptomatic patients or sparing patients from futile surgery," says Niklaus Schaefer, M.D., lead investigator at the University Hospital of Zurich in Zurich, Switzerland. "The positive impact on our patients is also significant. This serves as a model for further use of molecular imaging to assess neuroendocrine tumors."

Neuroendocrine tumors originate from cells of the neuroendocrine system, which regulates the effect of hormones in various organs throughout the body where hormones are active. This is especially the case in the lungs and gastrointestinal tract, where the rates of respiration and digestion are moderated by hormones. Many of these cancers are asymptomatic and metastatic, which means they can develop unnoticed and spread from their original location to other tissues and organs. Clinical decision-making can be a challenge when determining the most appropriate treatment for patients with these cancers.

In this study, investigators were looking at a molecular imaging method that combines positron emission tomography (PET), which provides information about physiological processes in the body, and computed tomography (CT), ideal for imaging structure. PET/CT was performed in conjunction with injection of an imaging probe that works by combining the radionuclide Gallium-68 (Ga-68) with a molecular compound that mimics hormones called somatostatins that regulate the neuroendocrine system. Upon injection, the probe begins interacting with neuroendocrine cellsespecially those within cancerous tumors, because they are more active than healthy cells. These biological processes show up as "hot-spots" on PET scans, letting clinicians know where neuroendocrine cancer is proliferating.

Results of the study indicated that PET/CT and Ga-68 DOTATATE was highly sensitive and specific for assessing neuroendocrine tumors and changed the course of treatment for a large number of patients. Prior to imaging, more than half of the 61 patients who were picked for the study were considered eligible for surgery to remove their cancer. The remaining 29 were determined to be inoperable. Subjects were then imaged using Gallium-68 DOTATATE PET/CT. After molecular imaging, about 36 percent of patients had a change in their management. Of those who were originally classified as operable, 14 were subsequently considered ineligible for surgery. For patients who were at first considered inoperable, 8 patients went on to have surgical resection of their tumors.

"This is the first prospective trial investigating the role of Gallium-68 DOTATATE in a multidisciplinary clinical setting and its impact on further patient management," says Schaefer. "Molecular imaging with this biomarker is already available in several centers around the world, and expansion of its use has the potential to help these patients and their treating physicians, who can use it to set up a clinical plan in one single investigation."

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PET imaging could lead to better care for neuroendocrine cancer

ScienceDaily (June 11, 2012) Out of control competitive aggression could be a result of a lagging neurotransmitter called dopamine, say researchers presenting a study at the Society of Nuclear Medicine's 2012 Annual Meeting. During a computer game against a putative cheating adversary, participants who had a lower capacity to synthesize this neurotransmitter in the brain were more distracted from their basic motivation to earn money and were more likely to act out with aggression.

For many people, anger is an almost automatic response to life's challenges. In clinical psychiatry, scientists look at not only the impact of aggressive behavior on the individual, their loved ones and the community but also the triggers in the brain that lead to aggressive response. The neurobiology of aggression is not well understood, but scientists are aware of a relationship between the neurotransmitter serotonin and certain aggressive behaviors. The objective of this study was to explore whether higher levels of another brain chemical called dopamine, involved in pleasure and reward, increased aggressive response in its subjects. To scientists' surprise, it was not as they first theorized.

"The results of this study were astonishingly opposite of what was previously hypothesized," says Ingo Vernaleken, M.D., lead author of the study and research scientist for the department of psychiatry at RWTH Aachen University in Aachen, Germany. "Subjects with more functional dopaminergic reward-systems were not more aggressive in competitive situations and could concentrate even more on the game. Subjects with lower dopaminergic capacity were more likely to be distracted by the cheating behavior."

In this study, 18 healthy adults in their twenties were tested for aggression using the psychological behavioral task known as the point subtraction aggression paradigm (PSAP). Participants were asked to play a computer game that required them to press a bar multiple times with the incentive of winning money, but they were also told that an adversary in the next room who is able to cheat may steal some of their winnings. What the paranoid participants did not know was that there was no adversary. The computer program is designed to perform randomized deductions of the subjects' monetary reward to simulate the cheating competitor.The participant had three choices to react: punish the cheater, shield against the adversary by repeatedly pressing a defense button, or continue playing the game in order to maximize their ability to win cash, which indicated resilience.

"The PSAP focuses on aggressive reaction within a competitive situation," says Vernaleken. "Aggression and its neurobiological mechanisms in humans have been only moderately investigated in the past. Furthermore, most of the previous studies mainly covered the more reactive part of aggression, which merely reflects impulsive behavior and appears to be associated merely with the serotonin system. This investigation focuses on the association with the dopaminergic reward-system, which reflects goal-directed aggression."

Subjects' brains were imaged using positron emission tomography, which provides a range of information about physiological functions inside the body, depending on the imaging probe used. In this investigation, F-18 FDOPA, a biomarker that lights up enzymes' ability to synthesize this transmitter, was used and the uptake of this drug in the brain was analyzed to gauge the correlation between the participants' dopamine synthesis capacity and aggressive behavior.

Results of the study showed a significant impact on aggressive response in areas in the brain where dopamine synthesis was present, especially in the basal ganglia, which among other functions include the motivation center. Minimized aggression was associated with higher dopamine levels in both the midbrain and the striatum, which plays a role in planning and executive function. People with greater capacity for dopamine synthesis were more invested in the monetary reward aspect of the PSAP, instead of acting in defense or with aggression against their perceived adversary, whereas subjects with lower capacities had a higher vulnerability to act either aggressive, defensive or both.

"Thus, we think that a well-functioning reward system causes more resilience against provocation," says Vernaleken. "However, we cannot exclude that in a situation where the subject would directly profit from aggressive behavior, in absence of alternatives, the correlation might be the other way around."

Further research is required to explore the link between dopamine and a range of aggressive behavior. More insight into these relationships could potentially lead to new psychological therapies and drug treatments to moderate or prevent aggressive response.

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Molecular imaging finds link between low dopamine levels and aggression