White matter hyperintensities in patients with multiple system atrophy

IntroductionAlthough white matter hyperintensities (WMHs) are prevalent in the elderly, the clinical significance and the underlying pathophysiological mechanisms of WMHs in neurodegenerative disorders have not been fully clarified.ObjectiveThe present study aimed to determine the degree of WMHs in patients with multiple system atrophy (MSA), and analyze the predisposing factors for WMHs.MethodsTwo raters blinded to clinical information assessed cerebrovascular lesions in brain MRIs from patients with MSA and age-matched controls. Patients with Parkinson’s disease (PD) were similarly studied as a disease control. The results obtained were compared with the clinical characteristics of the patients and statistically analyzed.ResultsWMHs in patients with MSA were statistically greater compared with PD patients or controls. There were no significant differences in either lacunar or territorial infarcts. Multiple linear regression analysis demonstrated that age, supine systolic blood pressure, and a drop in orthostatic blood pressure were significantly and independently correlated with WMH scores in MSA.ConclusionsThe present study suggests that white matter is differentially involved in MSA. In addition to aging, cerebral hypoperfusions caused by fluctuations of blood pressure may be a significant contributing factor to WMHs in MSA, although the possibility that degenerative processes occurring in oligodendrocytes may be associated with WMHs should not be excluded.     

Prognostic Value of BNP Reduction During Hospitalization in Patients With Acute Heart Failure

BackgroundPrognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF.Methods and ResultsWe studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission ? BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439–1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5–78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93–0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction.ConclusionsThe prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge.     

Anatomic dependency of phase shifts in the cerebral venous system of neonates at susceptibility-weighted MRI

Purpose:

To assess the anatomic variation and age‐related changes of phase shifts in the neonatal cerebral venous system at susceptibility‐weighted imaging (SWI).

Materials and Methods:

Thirty‐five neonates who had undergone SWI and who did not have any intracranial or systemic abnormalities were retrospectively assessed. Phase shifts in the veins in the deep gray matter and in the cortical veins in the frontal, rolandic, and parietal areas were measured and compared. Correlations between phase ratio (ratio of the phase shift in the vein in the deep gray matter to that in the cortical veins) and gestational age at birth, gestational age at magnetic resonance imaging (MRI), and age after birth were assessed.

Results:

Phase shift in the veins in the deep gray matter was significantly higher than those in the cortical veins (P < 0.01). Among the cortical veins, the venous phase shift in the rolandic area was significantly higher than those in the frontal and parietal areas (P < 0.01). There was a negative correlation between the phase ratio and the gestational age at MRI (Spearman ρ = ?0.35, P = 0.04).

Conclusion:

An anatomical variation in phase shifts was identified in the neonatal venous system. The observed reduction in phase shift differences between the veins in the deep gray matter and those in the cortex as gestational age at MRI increased may reflect brain development. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.

     

Effect of chelator conjugation level and injection dose on tumor and organ uptake of 111In-labeled MORAb-009, an anti-mesothelin antibody

Introduction

Radiolabeling of a monoclonal antibody (mAb) with a metallic radionuclide requires the conjugation of a bifunctional chelator to the mAb. The conjugation, however, can alter the physical and immunological properties of the mAb, consequently affecting its tumor-targeting pharmacokinetics. In this study, we investigated the effect of the amount of 2-(p-isothiocyanatobenzyl)-cyclohexyl-diethylenetriamine-pentaacetic acid (CHX-A″) conjugated to MORAb-009, a mAb directed against mesothelin, and the effect of MORAb dose on the biodistribution of ¹¹¹In-labeled MORAb-009.

Methods

We used nude mice bearing the A431/K5 tumor as a mesothelin-positive tumor model and the A431 tumor as a mesothelin-negative control. To find the optimal level of CHX-A″ conjugation, CHX-A″-MORAb-009 conjugates with 2.4, 3.5 and 5.5 CHX-A″ molecules were investigated. To investigate the effect of injected MORAb-009 dose on neutralizing the shed mesothelin in the circulation, biodistribution studies were performed after the intravenous co-injection of ¹¹¹In-labeled MORAb-009 (2.4 CHX-A″/MORAb-009) with three different doses: 0.2, 2 and 30 μg of MORAb-009.

Results

The tumor uptake in A431/K5 tumor was four times higher than that in A431 tumor, indicating that the tumor uptake in A431/K5 was mesothelin mediated. The conjugate with 5.5 CHX-A″ showed a lower isoelectric point (pI) and lower immunoreactivity (IR) than the 2.4 CHX-A″ conjugate. These differences were reflected in the biodistribution of the ¹¹¹In label. The ¹¹¹In-labeled MORAb-009 conjugated with 2.4 CHX-A″ produced higher tumor uptake and lower liver and spleen uptakes than the 5.5 CHX-A″ conjugate. The biodistribution studies also revealed that the tumor uptake was significantly affected by the injected MORAb-009 dose and tumor size. The 30-μg dose produced higher tumor uptake than the 0.2- and 2-μg doses, whereas the 30-μg dose produced lower liver and spleen uptakes than the 0.2-μg dose.

Conclusion

This study demonstrates that the number of chelate conjugation and the injected dose are two important parameters to achieve high tumor and low non-target organ uptake of ¹¹¹In-labeled MORAb-009. This study also suggests that the injected dose of mAb could be individualized based on the tumor size or the blood level of shed antigen in a patient to achieve the ideal tumor-to-organ radioactivity ratios.     

Preparation and biological evaluation of 3-[(76)Br]bromo-α-methyl-L-tyrosine, a novel tyrosine analog for positron emission tomography imaging of tumors

Introduction

3-[¹⁸F]fluoro-α-methyl-l-tyrosine ([¹⁸F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. FAMT analogs labeled with ⁷⁶Br, a positron emitter with a long half-life (t_1/2=16.1 h), could potentially be widely used as amino acid tracers for tumor imaging. In this study, 3-[⁷⁶Br]bromo-α-methyl-l-tyrosine ([⁷⁶Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors.

Methods

In this study, both [⁷⁶Br]BAMT and [⁷⁷Br]BAMT were prepared. The in vitro and in vivo stability of [⁷⁷Br]BAMT was evaluated by HPLC analysis. Cellular uptake and retention of [⁷⁷Br]BAMT and [¹⁸F]FAMT were evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in normal mice and in LS180 tumor-bearing mice, and the tumors were imaged with a small-animal PET scanner.

Results

[⁷⁷Br]BAMT was stable in vitro but was catabolized after administration in mice. Cellular accumulation and retention of [⁷⁷Br]BAMT were significantly higher than those of [¹⁸F]FAMT. In biodistribution studies, the tumor accumulation of [⁷⁷Br]BAMT was higher than that of [¹⁸F]FAMT. However, some level of debromination was seen, which caused more retention of radioactivity in the blood and organs than was seen with [¹⁸F]FAMT. PET imaging with [⁷⁶Br]BAMT enabled clear visualization of the tumor, and the whole-body image using [⁷⁶Br]BAMT was similar to that using [¹⁸F]FAMT.

Conclusions

[⁷⁷Br]BAMT showed high levels of tumor accumulation, and [⁷⁶Br]BAMT enabled clear visualization of the tumor by PET imaging. Although an improvement in stability is still needed, ⁷⁶Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors.     

Testicular cancer with inguinal lymph node metastasis in a patient with prior orchiopexy for undescended testis: a case report

A 36-year-old man referred to our hospital with the chief complaint of painful left inguinal mass and fever. He had undergone left orchiopexy for undescended testis at 10 years of age. With the suspicion of an incarceration of inguinal hernia, an operation was performed. However, there was no hernia sac, and only swelling inguinal lymph nodes were found. Pathological diagnosis of the nodes was metastatic embryonal carcinoma, with suspicion of testicular origin. As scrotal ultrasonography revealed a hypoehcoic mass within the left atrophic testis, left high orchiectomy was performed. Pathological diagnosis of the left testicular mass was seminoma. A definite diagnosis was left testicular cancer, mixed type of seminoma and embryonal carcinoma, with inguinal nodes metastasis, pT1N2M0. He received 3 courses of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, and there has been no sign of metastasis nor recurrence 18 months after the operation. To our knowledge, this is the 11th case in Japan of testicular cancer with inguinal node metastasis in a patient with prior orchiopexy for undescended testis.