(18) F-FDG PET/CT for initial staging in breast cancer patients - Is there a relevant impact on treatment planning compared to conventional staging modalities?

OBJECTIVE: To evaluate the impact of whole-body (18) F-FDG PET/CT on initial staging of breast cancer in comparison to conventional staging modalities. METHODS: This study included 102 breast cancer patients, 101 patients were eligible for evaluation. Preoperative whole-body staging with PET/CT was performed in patients with clinical stage ≥ T2 tumours or positive local lymph nodes (n = 91). Postoperative PET/CT was performed in patients without these criteria but positive sentinel lymph node biopsy (n = 10). All patients underwent PET/CT and a conventional staging algorithm, which included bone scan, chest X-ray and abdominal ultrasound. PET/CT findings were compared to conventional staging and the impact on therapeutic management was evaluated. RESULTS: PET/CT led to an upgrade of the N or M stage in overall 19 patients (19 %) and newly identified manifestation of breast cancer in two patients (2 %). PET/CT findings caused a change in treatment of 11 patients (11 %). This is within the range of recent studies, all applying conventional inclusion criteria based on the initial T and N status. CONCLUSIONS: PET/CT has a relevant impact on initial staging and treatment of breast cancer when compared to conventional modalities. Further studies should assess inclusion criteria beyond the conventional T and N status, e.g. tumour grading and receptor status. KEY POINTS: • PET/CT may be relevant in staging breast cancer patients at higher risk for metastases • PET/CT may modify the N and M stage in multiple patients • PET/CT may impact treatment planning in breast cancer patients.

Selective alpha7 nicotinic receptor activation by AZD0328 enhances cortical dopamine release and improves learning and attentional processes.

AZD0328, a novel spirofuropyridine neuronal nicotinic receptor partial agonist, was used to investigate the role of alpha7 neuronal nicotinic receptor (NNR) activation in the modulation of midbrain dopamine neuron function, cortical dopamine release and on two behavioral tasks known to be dependent on optimal levels of cortical dopamine. In vivo recordings from area 10 (ventral tegmental area) in rat brain showed an increased firing of putative dopamine neurons in response to low (0.00138 mg/kg) doses of AZD0328. Bursting patterns of dopamine neuron activity remained largely unchanged by application of AZD0328. In vivo microdialysis in awake rats showed an increase in extracellular prefrontal cortical dopamine in response to low doses of AZD0328. Compound-stimulated dopamine release showed an inverted dose effect relation that was maximal at the lowest dose tested (0.00178 mg/kg). Peak extracellular dopamine levels were reached 2h after dosing with AZD0328. Acquisition of operant responding with delayed reinforcement in rats was dose dependently enhanced by AZD0328 with a plateau effect measured at 0.003 mg/kg. This effect was blocked by pre-treatment of animals with the selective alpha7 antagonist methyllycaconitine. AZD0328 improved novel object recognition in mice over a broad range of doses (0.00178-1.78 mg/kg) and the compound effect was found to be absent in homozygous alpha7 KO animals. Together, these data indicate that selective interaction with alpha7 NNRs by AZD0328 selectively enhances midbrain dopaminergic neuronal activity causing an enhancement of cortical dopamine levels; these neurochemical changes likely, underlie the positive behavioral responses observed in two different animal models. Our results suggest selective alpha7 NNR agonists may have significant therapeutic utility in neurologic and psychiatric indications where cognitive deficits and dopamine neuron dysfunction co-exist.

Impact of Field Release of Genetically Modified Pseudomonas fluorescens on Indigenous Microbial Populations of Wheat.

In a field release experiment, an isolate of Pseudomonas fluorescens, which was chromosomally modified with two reporter gene cassettes (lacZY and Kan(supr)-xylE), was applied to spring wheat as a seed coating and subsequently as a foliar spray. The wild-type strain was isolated from the phylloplane of sugar beet but was found to be a common colonizer of both the rizosphere and phylloplane of wheat as well. The impact on the indigenous microbial populations resulting from release of this genetically modified microorganism (GMM) was compared with the impact of the unmodified, wild-type strain and a nontreated control until 1 month after harvest of the crop. The release of the P. fluorescens GMM and the unmodified, wild-type strain resulted in significant but transient perturbations of some of the culturable components of the indigenous microbial communities that inhabited the rhizosphere and phylloplane of wheat, but no significant perturbations of the indigenous culturable microbial populations in nonrhizosphere soil were found. Fast-growing organisms that did not produce resting structures (for example, fluorescent pseudomonads and yeasts) seemed to be most sensitive to perturbation. In terms of hazard and risk to the environment, the observed microbial perturbations that resulted from this GMM release may be considered minor for several reasons. First, the recombinant P. fluorescens strain caused changes that were, in general, not significantly different from those caused by the unmodified wild-type strain; second, perturbations resulting from bacterial inoculations were mainly small; and third, the release of bacteria had no obvious effects on plant growth and plant health.