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Background & Objective: Non-invasive brain stimulation (NIBS) might be a valuable therapeutic approach for neurological diseases by modifying the cortical activity in the human brain and promoting neural plasticity. Currently, researchers are exploring the use of NIBS on the cerebellum to promote functional neural changes in cerebellar disorders. In the presence of cerebellar dysfunction, several movement disorders, such as kinetic tremor, ataxia of gait, limb dysmetria and oculomotor deficits, become progressively more disabling in daily life, and no pharmacological treatments currently exist., Conclusion: In the present mini-review, we report the main evidence concerning the use of NIBS in three specific cerebellar dysfunctions, cerebellar ataxias (CA), essential tremor (ET) and ataxic cerebral palsy, in which abnormalities of neuroplasticity and cortical excitability can be important pathophysiological factors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Purpose: Imaging of the cardiac autonomic system with (123)I-metaiodobenzylguanidine (MIBG) is useful in the evaluation of patients with a variety of cardiac conditions, including heart failure (HF), but few data are available about the reproducibility of this technique. We assessed the observer reproducibility of the results from a low-dose (123)I-MIBG cardiac imaging protocol in patients with HF., Methods: A total of 74 patients (62 men, age 67 ± 10 years) with HF and left ventricular systolic dysfunction (ejection fraction 31 ± 7 %) underwent low-dose (111 MBq) planar and single-photon emission computed tomography (SPECT) (123)I-MIBG cardiac sympathetic imaging. The intraclass coefficient of correlation (ICC), Lin's concordance correlation coefficient, and Bland-Altman analysis were used to evaluate the intraobserver and interobserver reproducibility of early and late heart-to-mediastinum (H/M) ratios and of defect scores on SPECT images. The κ statistic was used to evaluate the concordance rates for the identification of patients with a low H/M ratio (<1.60) on late planar imaging., Results: The differences between measurements obtained twice by the same examiner and by two examiners were negligible for both early and late H/M ratios and for SPECT defect scores. These findings were confirmed by the results of Bland-Altman analysis, and ICC and Lin's coefficient values were excellent (>0.90) for all measurements. For the identification of patients with a low H/M ratio, the κ values were 0.90 for intraobserver concordance and 0.83 for interobserver concordance., Conclusion: The present study showed a high observer reproducibility of planar H/M ratios and SPECT defect scores using a low-dose (123)I-MIBG cardiac imaging protocol in patients with HF.

Aim: Technetium-99m 2-methoxy-isobutyl-isonitrile ([99mTc] MIBI) has been successfully used to study patients with multiple myeloma (MM). This tracer is also a substrate for P-glycoprotein (Pgp). Since Pgp overexpression is one of the primary mechanisms of multidrug resistance in MM, the aim of this study was to test whether [99mTc] MIBI could be an index of Pgp overexpression and function in MM and therefore predicts response to chemotherapy., Methods: Forty patients with MM (12 in stage I, 15 in stage II, and 13 in stage III) showing diffuse bone marrow [99mTc] MIBI uptake were included in the study. All patients underwent whole body scintigraphy at 10 and 60 minutes after i.v. injection of 555 MBq of [99mTc] MIBI. [99mTc] MIBI washout was measured, after decay correction, as: (10 minute counts/pixel minus 60 minute counts/pixel) divided by 10 minute counts/pixel, computed on a region of interest drawn on the thoracic spine (posterior projection), taking care of avoiding heart and splanchnic organs. Disease restaging was performed at a mean time of 32+/-20 months, and patients were considered to be in remission (complete or partial) or to show disease progression on the basis of a complete clinical and hematological evaluation., Results: Patients showing disease progression at restaging (n=26) had higher washout (19.3+/-9.8% vs 12.8+/-6.9%, p<0.05) than patients in remission (n=14). Disease free survival was significantly better in patients with lower washout of [99mTc] MIBI. No differences in therapeutic regimen and stage of disease at admission were found between the 2 groups. When patients treated with melphalan were excluded from the analysis, 87.5% of patients in remission had low washout., Conclusions: The present study suggests a potential role of [99mTc] MIBI washout in predicting response to chemotherapy in patients with MM.

Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging. In particular, cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with (111)In or (99m)Tc for the purpose of developing radiopharmaceuticals for in vivo CCK-B receptor imaging. Labeling of CCK8 with (111)In was achieved at the N-terminus of the peptide by adding, in solid phase, a glutamate coupled diethylenetriaminepentaacetic acid (DTPA) moiety through a glycine linker, yielding DTPA-Glu-G-CCK8. For labeling with (99m)Tc, the CCK8 peptide was modified at its N-terminus by introducing, in the following order--cysteine, glycine, and a diphenylphosphinopropionyl moiety--giving a 10-residue peptide derivative, Phos-GC-CCK8. A cell culture model was developed for the purpose of evaluating the binding properties of these two ligands. The human epidermoid carcinoma cell line, A431, was transfected with a plasmid containing the full coding sequence of the human CCK-BR under a strong viral promoter, obtaining a number of receptors in the range of 2-5 x 10(6) per cell. Control cells were transfected with vector alone. An animal tumor model utilizing these two cell lines was developed to evaluate the specificity of interaction with the CCK-BR and biodistribution properties of the compounds. CCK-BR positive and control cells were subcutaneously injected in opposite flanks of CD1 female nude mice in order to obtain xenografts differing only in their ability to express CCK-B receptors. High performance liquid chromatography (HPLC) and other chromatographic methods were utilized to assess stability of the radiolabeled compounds after injection. Both (111)In-DTPA-Glu-G-CCK8 and (99m)Tc-Phos-GC-CCK8 showed similar binding affinities for cultured CCK-BR expressing cells, with dissociation constants in the range of 20-40 nM. With the two xenograft approach, we were able to demonstrate specific interaction with the receptor of both CCK analogs in our animal model. The data obtained shows rapid specific localization of both compounds on the CCK-BR overexpressing xenografts. Both tracers show rapid plasma clearance of unbound peptide. Clearance of (111)In-DTPA-Glu-G-CCK8 appears to be preferentially through the kidneys, whereas (99m)Tc-Phos-GC-CCK8 clearance occurs both through kidneys and the hepatobiliary system. Both our labeling approaches appear adequate for clinical use of peptide based radiopharmaceuticals, although (99m)Tc-Phos-GC-CCK8 shows elevated accumulation in the gastrointestinal tract, which causes high background activity., (Copyright 2003 Wiley Periodicals, Inc.)