5-(123)I-A-85380 binding to the α4ß2-nicotinic receptor in mild cognitive impairment.

Treatments currently licensed for Alzheimer's dementia target cholinergic brain systems. In vivo nicotinic receptor binding may provide an early marker of illness and treatment suitability. In this pilot, we examined nine patients with amnestic mild cognitive impairment (MCI) and 10 age and education matched healthy volunteers with high resolution SPECT and the nicotinic receptor ligand 5-(123)I-A-85380. Uptake data were analysed using voxel-based techniques for group comparisons and regression analyses with cognitive impairment as covariates. MCI patients had discrete reductions in uptake in medial temporal cortex. Correlations with cognitive impairment were found in left temporo-parietal areas (Addenbrooke's Cognitive Examination) and bilateral temporo-limbic areas (Rey Auditory Verbal Learning Test), and right parahippocampal gyrus (Rey Complex Figure Test) within the patient group. In vivo nicotinic receptor binding appears to be sensitive to brain changes in MCI. Larger scale explorations of patients undergoing treatment will be necessary to evaluate its use in predicting or monitoring treatment response.

Assessment of 123I-FIAU imaging of herpes simplex viral gene expression in the treatment of glioma.

BACKGROUND: Herpes simplex virus 1716 (HSV1716), a selectively replication competent mutant of HSV1, is under investigation as an oncolytic viral therapy in human malignant glioma. As with similar therapies, a technique for measurement of viral replication and distribution over time following virus administration is required. Imaging expression of the HSV-thymidine kinase (HSV-tk) gene offers an opportunity for non-invasive assessment of viral distribution in living subjects. This is the first study to explore the use of HSV-tk as a reporter gene and radiolabelled thymidine analogue 5-[(123)I]iodo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil ((123)I-FIAU) as a marker substrate to non-invasively monitor HSV1716 replication in humans during treatment of high-grade glioma. METHODS: I-FIAU brain SPECT imaging was undertaken in eight patients receiving intra-tumoural injection of HSV1716, before and after administration of the virus. Baseline images were acquired 3 days prior to virus administration and between 1 and 5 days following virus administration. Region of interest analysis was used to investigate whether there was an increase in (123)I-FIAU concentration following virus administration due to HSV-tk expression. RESULT: Increased (123)I-FIAU accumulation due to HSV-tk expression was not detected in this study. The possible explanations for this finding are explored and design options for future studies are discussed.

Measurement of tumor "size" in recurrent malignant glioma: 1D, 2D, or 3D?

BACKGROUND AND PURPOSE: Tumor "size" is used internationally as a surrogate marker for overall survival when following current response assessment protocols (World Health Organization and Response Evaluation Criteria in Solid Tumors). With little evidence of a relationship between tumor "size" and survival in intrinsic brain tumors, this study was undertaken to investigate the predictive value of MR imaging-defined tumor size for survival in patients with recurrent malignant glioma and to compare the different measures of tumor size used in these current response assessment protocols. METHODS: Volumetric, bidimensional, and unidimensional measurements of tumor size were made using baseline contrast-enhanced T1-weighted images of 70 patients with recurrent malignant glioma receiving intravenous chemotherapy. Cox's proportional hazards model was used to investigate the prognostic importance of tumor size using survival as the end point. Further statistical analysis was undertaken to investigate the relationship between the different measurement techniques. RESULTS: Only the volumetric measurement of tumor size was found to be predictive of survival in recurrent malignant glioma on both univariate and multivariate analysis. Furthermore, analysis demonstrated that the unidimensional and bidimensional measures of tumor were not comparable with the more accurate and direct volumetric measurement. CONCLUSION: Indirect unidimensional and bidimensional measurement techniques do not have a significant association with overall survival or adequately assess tumor size in recurrent malignant glioma. These findings have serious implications about the validity of using current response assessment protocols in therapy trials for recurrent malignant glioma.

Self-stunning in thyroid ablation: evidence from comparative studies of diagnostic 131I and 123I.

Twenty-six patients who had undergone recent surgery for differentiated thyroid cancer were investigated using iodine-131 iodide (120 MBq). Uptake in the thyroid bed was measured at 3 days using a dual-head gamma camera. An ablation activity of 131I iodide (4,000 MBq) was administered 3-38 (median 14) days later and uptake in the thyroid bed measured once or twice, 1-3 days post therapy. For measurements post therapy, the gamma camera was operated in the high-count rate mode with appropriate correction factors to compensate for any count loss. A further 16 patients were given iodine-123 iodide (200 MBq) as the diagnostic agent and uptake was measured at 24 h. The ablation activity was administered 5-47 (median 19) days later and uptake again measured at 24 h. In some cases, a further measurement of uptake was made within the period 1-3 days post therapy. Reduced uptake of the therapeutic administration ( P<0.001) was observed in all 26 patients given diagnostic 131I, with a median value of 32.8% (range 6%-93%) of the uptake in the diagnostic study. In the patients given diagnostic 123I, reduced uptake of the ablative radioiodine was observed in 15 of the 16 patients ( P<0.001), and overall the median value was 58.8% (range 17%-130%) of the diagnostic uptake. In one case the uptake post therapy was increased. The stunning observed in the group given 123I was significantly less ( P<0.001) than in the group given 131I. In the patients given diagnostic 131I, stunning appeared to increase in severity the longer the time interval between the diagnostic and therapeutic radionuclides, for intervals up to 25 days. Thereafter, there seemed to be some recovery of uptake capability. Overall there was no evidence of a large rapid loss of radionuclide from the thyroid bed 1-3 days post therapy. The stunning observed using 123I could not be explained by errors in the estimation of relative uptake due to different tissue absorption of the 131I and 123I photons, nor by the radiation dose delivered by the 123I. However, the ablative 131I itself may cause stunning because the cumulated activity, over the first few hours of uptake, is not insignificant when compared with all the cumulated activity from a diagnostic administration of 131I. The resultant radiation dose to the thyroid remnant, as the therapeutic radioiodine is being taken up, may be sufficient to inhibit the uptake process, thus leading to a reduction in maximum uptake when compared with that of a diagnostic activity of radioiodine.

MRI safety review.

Magnetic resonance is an extremely powerful imaging tool which does not expose patients to ionizing radiation. However, there are risks associated with the MR environment which all staff must be aware of and eliminate. The aim of this article is to highlight the well known and not so well known potentially adverse interactions. Although many safety investigations have been carried out at up to 1.5T, the reader will be reminded that as many centres install magnets of 2.0T and above, much of the current safety literature cannot be simply extrapolated to these higher field strengths and further investigations will be required to reassure staff and patients of the limits of their safe use.