Positron emission tomography

Cannabinoid System Dysregulation in PTSD.

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Patients with posttraumatic stress disorder have more cannabinoid receptors and fewer endocannabinoids in plasma than people without the disorder.

The consolidation of emotionally aversive memories that underlies the development of posttraumatic stress disorder (PTSD) occurs via a synergistic interaction between stress-induced cortisol and norepinephrine inputs into the amygdala, which are modulated by endocannabinoid signaling. These researchers examined availability of cannabinoid 1 (CB1) receptors during resting positron emission tomography in 25 untreated PTSD patients, 12 non-PTSD trauma controls, and 23 healthy controls. Cortisol and other possible biomarkers were also measured.

Compared with healthy and trauma controls, PTSD patients had significantly more CB1receptors (20% and 14% higher, respectively) both overall and in CB-rich and fear-relevant hippocampal, amygdala, and corticostriatal areas. PTSD was associated with lower plasma levels of the endocannabinoid anandamide (53% and 58% lower). Both effects were more pronounced in women. Cortisol levels were lower in PTSD patients and trauma controls than in healthy controls. Use of all three biomarkers enabled accurate classification of 85% of PTSD cases.

Comment: This study is the first to document abnormalities in cannabinoid signaling in PTSD, with lower endocannabinoid levels likely driving the greater CB1 receptor availability. The findings are consistent with reports of frequent self-medication with cannabis in PTSD patients. The authors warn against cannabis self-medication; note that chronic use of CB agonists down-regulates CB receptors, thus producing a depressive phenotype over time and aggravating substance dependence; and suggest that medications blocking anandamide degradation or uptake are much more likely to restore CB1 system integrity. Cannabis self-medication in anxious patients might provide short-term relief, but is likely to result in problems similar to those seen with overuse of benzodiazepines to treat anxiety.

 

Source:  Journal Watch Psychiatry

 

Targeted molecular imaging in oncology.

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Improvement of scintigraphic tumor imaging is extensively determined by the development of more tumor specific radiopharmaceuticals. Thus, to improve the differential diagnosis, prognosis, planning and monitoring of cancer treatment, several functional pharmaceuticals have been developed. Application of molecular targets for cancer imaging, therapy and prevention using generator-produced isotopes is the major focus of ongoing research projects. Radionuclide imaging modalities (positron emission tomography, PET; single photon emission computed tomography,

SPECT) are diagnostic cross-sectional imaging techniques that map the location and concentration of radionuclide-labeled radiotracers.

99mTc- and 68Ga–labeled agents using ethylenedicysteine (EC) as a chelator were synthesized and their potential uses to assess tumor targets were evaluated.

99mTc (t1/2 = 6 hr, 140 keV) is used for SPECT and 68Ga (t1/2 = 68 min, 511 keV) for PET. Molecular targets labeled with Tc-99m and Ga-68 can be utilized for prediction of therapeutic response, monitoring tumor response to treatment and differential diagnosis. Molecular targets for oncological research in (1) cell apoptosis, (2) gene and nucleic acid-based approach, (3) angiogenesis (4) tumor hypoxia,and (5) metabolic imaging are discussed. Numerous imaging ligands in these categories have been developed and evaluated in animals and humans. Molecular targets were imaged and their potential to redirect optimal cancer diagnosis and therapeutics were demonstrated.

Source: http://www.jsnm.org

 

PET and Prognosis in Follicular Lymphoma.

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A negative posttreatment PET scan was associated with improved survival in patients with advanced-stage disease.

Complete remission with a negative positron emission tomography (PET) scan after front-line induction chemotherapy is associated with improved outcomes in Hodgkin lymphoma and diffuse large B-cell lymphoma. To assess the prognostic value of PET in follicular lymphoma (FL), European investigators conducted a prospective, multicenter trial involving 117 patients with advanced-stage, high–tumor burden FL who were treated with six cycles of R-CHOP (rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisone) followed by two additional doses of rituximab. PET scans were performed at baseline, after cycle four (PETC4), and at completion of therapy (PETC8). Independent central review of PET response was performed by three nuclear medicine radiologists and classified by established criteria (Deauville 5-point scale). No treatment modifications were made based on PET findings.

Results were as follows:

  • Of 106 patients who underwent PETC8 imaging, 83 (78%) had negative results.
  • Of 78 patients with negative PETC4 results, 6 (8%) reverted to a positive posttreatment scan.
  • Of 26 patients with positive PETC4 results, 17 (65%) remained positive on PETC8.
  • When comparing PET response to standard computed tomography–based assessment, 53 of 54 patients (98%) with complete remissions were PET-negative, whereas 10 of 20 patients (50%) with complete remissions unconfirmed (CRu) and 9 of 26 patients (35%) with partial remission (PR) remained PET-positive.
  • Patients with negative posttreatment PET had improved 2-year overall survival versus those with a positive scan (100% vs. 88%; P=0.01).
  • Progression-free survival was improved for those with negative versus positive PETC4 or PETC8.

Comment: This is the first prospective study to demonstrate a prognostic benefit for negative posttreatment PET in FL. The predictive value was independent of both low-risk and high-risk FLIPI (Follicular Lymphoma International Prognostic Index) scores. The authors recommend that only posttreatment PET rather than interim PET be used and that scan use be reserved for CRu and PR patients. Confirmation of these results in additional prospective trials will be important, as will careful application of standardized PET response criteria and PET response–based treatment algorithms.

Source: Journal Watch Oncology and Hematology

 

Accuracy of Florbetapir PET Imaging in Alzheimer Disease.

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The imaging modality is highly accurate, but its role in diagnosis and its social implications need consideration.

Imaging biomarkers have been studied as a means of detecting amyloid-beta (Aβ) pathology in vivo. One such marker, the FDA-approved positron emission tomography (PET) amyloid imaging agent [18F]florbetapir, previously demonstrated correlation with autopsy findings of Aβ plaque in 35 people with baseline cognitive status ranging from normal to severely demented (JW Neurol Feb 22 2011). Now, the same investigators have conducted a manufacturer-sponsored follow-up study with 24 additional cases that came to autopsy, to assess the accuracy of florbetapir PET imaging.

Of the 59 patients, 46 came to autopsy within 12 months after imaging; the remainder did so within 2 years. The primary analysis compared ratings of florbetapir PET images by five physician readers with binary histopathological findings at autopsy (no or few Aβ plaques vs. moderate or frequent plaques). The majority rating by the five readers was 92% sensitive and 100% specific for imaging done within 2 years of autopsy; it was 96% sensitive and 100% specific within 1 year of autopsy. Overall, individual reader accuracy was similar to the majority-rating accuracy, and semiquantitative analyses of PET images were also highly accurate.

Comment: This study offers encouragement to physicians and families who seek a definitive diagnosis of Alzheimer disease (AD) in vivo so that they can make informed decisions about participation in clinical trials and other major life decisions such as planning for family needs. However, implications for insurability, employment, behavioral health, and quality of life need to be carefully considered before proceeding with amyloid imaging, as the results may be perceived as being similar to those of genetic testing in AD and other neurodegenerative diseases. Although florbetapir has been approved by the FDA, many questions remain regarding its role in diagnosis, interpretation of a patient’s images by an inexperienced reader, and reimbursement (or lack thereof) by insurance providers.

Source: Journal Watch Neurology