Enhancement of biological effectiveness of carbon-ion beams by applying a longitudinal magnetic field

Abstract

Purpose: A magnetic field longitudinal to an ion beam will potentially affect the biological effectiveness of the radiation. The purpose of this study is to experimentally verify the significance of such effects.

Methods and materials: Human cancer and normal cell lines were exposed to low (12?keV/μm) and high (50?keV/μm) linear energy transfer (LET) carbon-ion beams under the longitudinal magnetic fields of B_// = 0, 0.1, 0.2, 0.3, or 0.6 T generated by a solenoid magnet. The effects of the magnetic fields on the biological effectiveness were evaluated by clonogenic cell survival. Doses that would result in a survival fraction of 10% (D₁₀s) were determined for each cell line and magnetic field.

Results: For cancer cells exposed to the low (high)-LET beams, D₁₀ decreased from 5.2 (3.1) Gy at 0 T to 4.3 (2.4) Gy at 0.1 T, while no further decrease in D₁₀ was observed for higher magnetic fields. For normal cells, decreases in D₁₀ of comparable magnitudes were observed by applying the magnetic fields.

Conclusions: Significant decreases in D₁₀, i.e. significant enhancements of the biological effectiveness, were observed in both cancer and normal cells by applying longitudinal magnetic fields of B_// ≥?0.1 T. These effects were enhanced with LET. Further studies are required to figure out the mechanism underlying the observed results.     

Radioiodinated peptide probe for selective detection of oxidized low density lipoprotein in atherosclerotic plaques

IntroductionDespite the significant effort in developing radioprobes for atherosclerosis, few have low molecular weight. Oxidized LDL (OxLDL), a highly proinflammatory and proatherogenic factor that is abundant in atherosclerotic plaques, plays a pivotal role in plaque destabilization, which makes OxLDL a relevant probe target. We developed a radioiodinated short peptide, AHP7, as a low molecular weight probe for specific OxLDL imaging and evaluated its utility using myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits (WHHLMI).Methods[¹²⁵I]AHP7 was designed and synthesized based on the sequence of Asp-hemolysin, an OxLDL binding protein extracted from Aspergillus fumigatus. In vitro binding studies with OxLDL having varying degrees of oxidation were performed. Radioactivity accumulation in the aorta was measured 30 min post-administration in rabbits. Autoradiography and histological studies were performed using serial aorta sections. A radioiodinated scrambled peptide ([¹²⁵I]AHP scramble) was used as a negative control.Results[¹²⁵I]AHP7 bound to OxLDL in proportion to the degree of oxidation (R = 0.91, P < 0.0001) and was inhibited by unlabeled AHP7 in a concentration-dependent manner. The aorta accumulation level and aorta/blood and aorta/muscle ratios of [¹²⁵I]AHP7 in WHHLMI were 2.8-, 1.3- and 1.8-fold higher, respectively, than those in control rabbits (P < 0.001). Co-administration of AHP7 significantly reduced [¹²⁵I]AHP7 radioactivity in aorta sections (P < 0.0001). Regional radioactivity levels in the aorta sections showed nonuniformity but similarity to the immunohistochemical OxLDL density.ConclusionsThe potential of radioiodinated AHP7 for selectively imaging OxLDL was demonstrated both in vitro and in vivo.     

Comparison of the Central Adrenal Vein and the Common Trunk of the Left Adrenal Vein for Adrenal Venous Sampling

PurposeTo compare left adrenal venous sampling (AVS) in two locations: the central adrenal vein and the common trunk.Materials and MethodsA total of 22 patients (12 men and 10 women; mean age, 50 y; range, 26–65 y) who were suspected of having primary aldosteronism (PA) and underwent successful AVS with cortisol concentration measurement and/or venography between November 2010 and August 2011 were retrospectively analyzed. In regard to the left adrenal vein, collections were done at two locations: at the common trunk below the confluence of the inferior phrenic vein and at the central adrenal vein, which was above the confluence. The effects of the inflow from the inferior phrenic vein on plasma aldosterone and cortisol levels were analyzed.ResultsEight patients had bilateral hypersecreting lesions and 13 had a unilateral lesion. One was diagnosed as having secondary hypertension other than PA. The median cortisol levels below and above the confluence were 129 μg/dL (range, 21–400 μg/dL) and 215 μg/dL (range, 21–690 μg/dL), respectively. The median aldosterone levels were 2,120 pg/mL (range, 164–42,700 pg/mL) and 4,275 pg/mL (range, 119–59,000 pg/mL), respectively. The median aldosterone/cortisol (A/C) ratios were 244 (range, 34–2,401) and 278 (range, 25–2,251), respectively. Cortisol and aldosterone levels were significantly higher above the confluence (P = .0050 and P = .0003, respectively), whereas the A/C ratio showed no significant difference (P = .12).ConclusionsAlthough higher levels of cortisol and aldosterone were obtained upstream, A/C ratio was not significantly different between the central adrenal vein and the common trunk.     

Successful human islet isolation utilizing recombinant collagenase

The enzymatic dissociation of acinar tissue by collagenase is a substantial step in the isolation of pancreatic islets. Although essential collagenase components have been purified, the variability in the activity of different batches limits long-term reproducibility of isolation success. The utilization of purified recombinant proteases would solve this problem. In the present study, pancreases from multiorgan donors were dissociated by means of digestion-filtration using either Liberase HI (n = 51) or a recombinant collagenase blend (n = 25). No significant differences were found regarding islet yield before and after purification, the percent of exocrine-attached islets, and final purity. However, the ratio between islet equivalents and islet numbers indicated a lesser fragmentation in islets isolated with recombinant collagenase (P < 0.01). In contrast, viability was slightly higher in islets isolated with Liberase (92.3 +/- 0.8 vs. 85.6 +/- 2.9%; P < 0.05). Insulin release during static glucose incubation was not different between experimental groups. Islet transplantation into diabetic nude mice resulted in sustained normoglycemia in either group until the graft was removed. These results demonstrated that viable human islets can be isolated using recombinant collagenase. Final optimization of this enzyme blend would offer continuous reproducibility of isolation success.     

Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide transporter.

H+/peptide transporter, PEPT1, is functionally expressed in some human cancer cell lines and might be a candidate molecular target for detection of cancers in vivo using PET. The aim of the present study was to establish a novel tumor-imaging technology using a PET tracer targeted to H+/peptide transporter(s). We also compared the tracer with 18F-FDG, focusing on the specificity of their accumulation between tumor and inflammatory tissues. METHODS: A dipeptide PET tracer, 11C-glycylsarcosine (11C-Gly-Sar), was injected intravenously into athymic mice transplanted with human pancreatic, prostate, and gastric cancer cells. The distribution patterns of 11C-Gly-Sar and 18F-FDG in the tumor-bearing mice, and in mice with inflammatory tissue, were assessed by imaging with a positron planar imaging system (PPIS). Tissue distributions of tracer radioactivity were also measured. The expression levels of PEPT1 and PEPT2 (PEPTs) proteins in tumor xenografts and inflammatory tissue were examined by immunohistochemical analysis. The messenger RNA expression levels of PEPTs in 58 available cancer cell lines were quantified by means of real-time polymerase chain reaction. RESULTS: All 3 tumor xenografts were well visualized with the PPIS after injection of 11C-Gly-Sar. Expression of PEPTs in those xenografts was confirmed by immunohistochemical analysis. Tumor-to-blood concentration ratios of 11C-Gly-Sar increased in a time-dependent manner and were much higher than unity. Most of the radioactivity found in the tumor tissue was recovered as the intact tracer. These results indicated that 11C-Gly-Sar was taken up by the PEPTs in tumor xenografts. It is noteworthy that 11C-Gly-Sar was minimally present in inflammatory tissues that expressed no PEPT1 or PEPT2 protein, whereas 18F-FDG was highly accumulated, with the values of the selectivity index being >25.1 and 0.72 for 11C-Gly-Sar and 18F-FDG, respectively. The mRNAs of PEPT1 and PEPT2 were expressed in 27.6% and 93.1%, respectively, of the cancer cell lines examined in the present study. CONCLUSION: The present study indicates that 11C-Gly-Sar is a promising tumor-imaging agent and is superior to 18F-FDG for distinguishing between tumors and inflammatory tissue. Because PEPTs were ubiquitously expressed in various types of tumor cells examined, 11C-Gly-Sar could be useful for the detection of many types of cancers.     

Near-infrared spectroscopy for noninvasive evaluation of chest wall ischemia immediately after left internal thoracic artery harvesting

OBJECTIVE: The conclusions remain controversial about whether the sternal blood flow is preserved or diminished after internal thoracic artery (ITA) harvesting for coronary artery bypass grafting (CABG), especially in diabetic patients. We investigated the blood supply of the chest wall noninvasively using near-infrared spectroscopy (NIRS) immediately after CABG. METHODS: The study group comprised 30 patients who underwent CABG using a skeletonized left ITA through median sternotomy. As a control group, three nondiabetic patients undergoing valve surgery through median sternotomy were also included. On arrival of the patient in the intensive care unit immediately after surgery, two reflectance sensors were placed on the bilateral parasternal regions at the fourth intercostal space to record regional oxygen saturation (rSO(2)) and hemoglobin index (HbI) continuously approximately for 17 h. RESULTS: The differences in right and left values (R-L rSO(2) and R-L HbI) were significantly greater in the diabetic patients than in the nondiabetic patients (3.74% +/- 2.47% vs. 1.98% +/- 1.67 %, p = 0.036; and 0.28 +/- 0.19 vs. 0.13 +/- 0.13, p = 0.020). The R-L HbI was significantly greater in the on-pump patients than in the off-pump patients, although there was no significant difference in R-L rSO(2). Both R-L rSO(2) and R-L HbI were similar among the control, nondiabetic, and off-pump patients. CONCLUSION: The technique of NIRS enables noninvasive, continuous monitoring of chest wall perfusion immediately after ITA harvesting. Our study using NIRS showed a decrease in blood flow and oxygen metabolism of the hemisternum after LITA harvest in diabetic CABG patients.     

A simple and safe operation method for brachiocephalic artery aneurysms

A 64-year-old man was referred to our hospital due to dyspnea and fever. The chest computed tomogram revealed a 60-mm aneurysm of the brachiocephalic artery with mural thrombus. The aneurysm of the brachiocephalic artery and the right subclavian artery were exposed through only median sternotomy. Cardiopulmonary bypass with synchronized pulsatile perfusion was established with the ascending aorta and bi-caval cannulation. A mean arterial pressure was kept at between 60 and 70 mmHg with the unloaded beating heart. Mild hypothermia was induced (blood temperature 27 degrees C, nasopharyngeal temperature 32 degrees C). The brachiocephalic artery, right carotid artery, and right subclavian artery were clamped when nasopharyngeal temperature was 32 degrees C after decreasing blood temperature to 27 degrees C. After opening the aneurysm, the mural thrombus and calcified aneurysmal wall were removed. First, an ascending aorta to the right common carotid artery bypass was performed using a 16-8 mm Y- prosthetic graft with side-clamp forceps. After the anastomosis, the right side cerebral perfusion was restarted and the patient was rewarmed. Then the right subclavian artery was anastomosed in an end-to-end fashion. The duration of the right side cerebral circulatory arrest was 30 minutes. The patient left hospital seven days after the operation.     

Spontaneous resorption in recurrent intradural lumbar disc herniation. Case report

The authors report a case of spontaneous resorption of intradural disc material in a patient with recurrent intradural lumbar disc herniation and review magnetic resonance (MR) imaging and histopathological findings. Intradural lumbar disc herniation is rare, and most patients with this condition require surgical intervention due to severe leg pain and vesicorectal disturbance. In the present case, however, the recurrent intradural herniated mass had completely disappeared by 9 months after onset. Histological examination of intradural herniated disc tissue demonstrated infiltrated macrophages and angiogenesis within the herniated tissue, and Gd-enhanced MR images showed rim enhancement not only at the initial presentation, but also at recurrence. The authors conclude that when rim enhancement is present on Gd-enhanced MR images, there is a possibility of spontaneous resorption even though the herniated mass may be located within the intradural space. Moreover, when radiculopathy is controllable and cauda equina syndrome is absent, conservative therapy can be selected.     

A gastric duplication cyst with an aberrant pancreatic ductal system: report of a case

We report an extremely rare case of a gastric duplication cyst together with an aberrant pancreatic ductal system, which communicated with the stomach rather than the pancreatic ductal system with no evidence of pancreatitis. A 46-year-old woman developed severe abdominal pain after a 10-year history of occasional mild abdominal pain. Upper gastrointestinal barium radiography showed a rigidity of the stomach wall, and gastroscopy revealed a fistula orifice at a greater curvature of the gastric body. Subsequent endoscopic suction of mucous secretion from within the fistula provided immediate pain relief. Abdominal computed tomography and ultrasonography showed a cystic mass contiguous with the stomach wall. Surgical exploration revealed an uncommon anomaly of a gastric duplication cyst with the aberrant pancreatic lobe. The patient made an uneventful recovery and remains well 4 years after surgery. We also herein review ten other similar cases of this uncommon congenital anomaly reported in the literature. Received: August 20, 2001 / Accepted: January 8, 2002