[Manufacture and Utilization of a Low-level Radioactive 68Ge/68Ga Generator in a Radiochemistry Laboratory Course].

The low-level radioactivity of a (68)Ge/(68)Ga generator is a suitable tool for measuring radioactive growth and decay after (68)Ga milking due to their desirable nuclear decay properties, such as the EC decay of (68)Ge with no γ-ray emission andthe ß(+) decay of (68)Ga with a weak γ-ray emission. To experience andund erstandrad ioactive equilibrium during a university laboratory course, we surveyedandtestedthe production of a small amount of (68)Ge and set up educational programs to manufacture a (68)Ge/(68)Ga generator for measuring the growth andd ecay of (68)Ga. The irradiation of natGa with 25 µA of a 30 MeV proton beam from a cyclotron for 4 h yields ca. 111 MBq of (68)Ge, which was sufficient to supply to several universities. For use as the adsorbent of the generator column, particles of hydrated tin (VI) oxide were prepared from precipitated tin hydroxide gel. Repeated elution of (68)Ga from the handmade (68)Ge/(68)Ga generator gave constant amounts of (68)Ga with acceptable breakthrough of (68)Ge. The feedback from the student's experience with the (68)Ge/(68)Ga generator was evaluatedby annual questionnaire surveys, which were given to all students taking the course every year from 2012 to 2014. It has been made clear that more than half of the students were interested in the (68)Ge/(68)Ga generator program, andthis interest increasedfrom 54.9%in 2012 to 78.6%in 2014. A low-level radioactive (68)Ge/(68)Ga generator is thus expectedto be a suitable experimental tool for demonstrating the phenomenon of radioactivity to students in an intriguing way.

Reduced nasal transport of insulin-like growth factor-1 to the mouse cerebrum with olfactory bulb resection.

Although the olfactory nerve is involved in nasal transport of insulin-like growth factor-1 (IGF-1) to the brain, to our knowledge there have been no direct assessments of the effects of olfactory nerve damage on this transport. To determine whether olfactory bulb resection resulted in reduced transport of nasally administered human recombinant IGF-1 (hIGF-1) to the cerebrum, we measured the uptake of nasally administered iodine-125 hIGF-1 ((125)I-hIGF-1) in the cerebrum as a percentage of that in the blood in male ICR mice subjected to left olfactory bulb resection (model mice) and in sham-operated male ICR mice (control mice). Phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204)/(Thr185/Tyr187) as a percentage of total ERK 1/2 in the left cerebrum was also assessed by using enzyme-linked immunosorbent assay after nasal administration of hIGF-1. Uptake of nasally administered (125)I-hIGF-1 in the cerebrum as a percentage of that in the blood was significantly lower in the model group than in the control group 30min after nasal administration of hIGF-1. Unilateral olfactory bulb resection prevented nasally administered hIGF-1 from increasing the phosphorylation of ERK 1/2 in the mouse cerebrum in vivo. These findings suggest that olfactory bulb damage reduces nasal transport of hIGF-1 to the brain in vivo.

Assessment of olfactory nerve by SPECT-MRI image with nasal thallium-201 administration in patients with olfactory impairments in comparison to healthy volunteers.

PURPOSE: The aim of this study was to assess whether migration of thallium-201 ((201)Tl) to the olfactory bulb were reduced in patients with olfactory impairments in comparison to healthy volunteers after nasal administration of (201)Tl. PROCEDURES: 10 healthy volunteers and 21 patients enrolled in the study (19 males and 12 females; 26-71 years old). The causes of olfactory dysfunction in the patients were head trauma (n = 7), upper respiratory tract infection (n = 7), and chronic rhinosinusitis (n = 7). (201)TlCl was administered unilaterally to the olfactory cleft, and SPECT-CT was conducted 24 h later. Separate MRI images were merged with the SPECT images. (201)Tl olfactory migration was also correlated with the volume of the olfactory bulb determined from MRI images, as well as with odor recognition thresholds measured by using T&T olfactometry. RESULTS: Nasal (201)Tl migration to the olfactory bulb was significantly lower in the olfactory-impaired patients than in healthy volunteers. The migration of (201)Tl to the olfactory bulb was significantly correlated with odor recognition thresholds obtained with T&T olfactometry and correlated with the volume of the olfactory bulb determined from MRI images when all subjects were included. CONCLUSIONS: Assessment of the (201)Tl migration to the olfactory bulb was the new method for the evaluation of the olfactory nerve connectivity in patients with impaired olfaction.

Evaluation of the olfactory nerve transport function by SPECT-MRI fusion image with nasal thallium-201 administration.

PURPOSE: The aim of this study was to visualize the human olfactory transport pathway to the brain by performing imaging after nasal thallium-201 ((201)Tl) administration. PROCEDURES: Healthy volunteers were enrolled in this study after giving informed consent (five males, 35-51 years old). The subjects were nasally administered (201)TlCl into either the olfactory cleft. Twenty-four hours later, uptake of (201)Tl was detected by a single photon emission computed tomography (SPECT)/X-ray computed tomography hybrid system. For each subject, an MRI image was obtained and merged with the SPECT image. RESULTS: The peak of the (201)Tl uptake entered into the olfactory bulb in the anterior skull base through the cribriform lamina 24 h after nasal administration of (201)Tl. No participant had olfactory disturbance after treatment. CONCLUSIONS: Nasal (201)Tl administration was safely used to assess the direct pathway to the brain via the nose in healthy volunteers with normal olfactory threshold.

[Result of the onsite dosimetry and questioning about quality assurance/ quality control of radiotherapy in the Hokuriku area - a comparison with past results -].

PURPOSE: To analyze temporal changes in human resources in the radiotherapy section, quality assurance/quality control (QA/QC) and dose difference for radiotherapy in the Hokuriku area based on the results of past investigations and our investigation. METHOD: We visited radiotherapy sections of 17 hospitals in the Hokuriku area (5 in Toyama, 9 in Ishikawa and 3 in Fukui) to measure the dose at the reference point of a linear accelerator (LINAC), as we asked questions to a radiotherapist about human resources, QA/QC of LINAC, etc. We compared our results with past reports (1992 to 2007) on the dose difference, human resources and frequency of dose monitor system calibration. RESULTS: The number of physicians has not changed since 1999, but the number of radiotherapists was significantly increased. Weekly dose monitor system calibration has been achieved in 80% of the institutions in our survey. This percentage was significantly higher than in the past surveys. The dose difference distribution from our onsite dosimetry did not significantly differ from that from the onsite dosimetry in 2007. 91% of the institutions have accomplished within 2% of the dose difference. CONCLUSION: We found that the number of physicians has not increased since 1999, but the number of radiotherapists has increased. We conclude that the increment of radiotherapists led to 80% achievement of the weekly dose monitor system calibration. Almost all institutions in Hokuriku area have properly performed QA of the dose monitor system.

Use of thallium transport to visualize functional olfactory nerve regeneration in vivo.

OBJECTIVE: To image olfactory nerve regeneration in vivo using a high-resolution gamma cam- era and radiography after nasal administration of thallium-201 (olfacto-scintigraphy). METHODS: Six Wistar rats were trained to avoid the smell of cycloheximide as a test of olfactory function. The olfactory nerve fibers of 3 rats were then carefully transected bilaterally with a Teflon knife, avoiding damage to the olfactory bulbs. The remaining 3 rats underwent sham operations and were used as controls. Steel wires were implanted in the left olfactory bulb of each rat for locating the bulbs with plain X-rays. The rats were assessed 2, 14, 28, and 42 d after the olfactory nerve transection or sham operation for their ability to detect odours and for transport of 201Tl to the olfactory bulb area 8 h after nasal administration of 201Tl. RESULTS: Both transport of 201Tl to the olfactory bulb area (p < 0.04) and ability to detect odours (p < 0.04) significantly increased with a time course after olfactory nerve transection. CONCLUSION: 201Tl transport to the olfactory bulb may be useful to visually assess olfactory ability in vivo. We plan to test olfacto-scintigraphy clinically by nasal administration of 201Tl in patients with posttraumatic olfactory loss.

Odor detection ability and thallium-201 transport in the olfactory nerve of traumatic olfactory-impaired mice.

Although olfactory nerve damage is a contributing factor in the diagnosis of posttraumatic olfactory loss, at present, there are no methods to directly assess injury to these nerves. We have shown that following olfactory nerve injury in mice, thallium-201 (201 Tl) transport from the nasal cavity to the olfactory bulb decreases. To determine if olfactory function after nerve injury could be assessed with nasal administration of 201 Tl, we measured the correlation between odor detection ability (ODA) and the rate of transport of 201 Tl in olfactory nerves. Both ODA and 201 Tl transport were measured after bilateral olfactory nerve transection for a 4-week period. Cycloheximide solution was used for ODA against tap water. 201 Tl transport was measured as the ratio of radioactivity in the nasal cavity and olfactory bulb with gamma spectrometry. There was a significant correlation between ODA and the rate of 201 Tl transport in the olfactory nerve. These findings suggest that olfactory function after nerve injury can be objectively evaluated with the nasal administration of 201 Tl.

alpha(v)beta(3) Integrin-targeting radionuclide therapy and imaging with monomeric RGD peptide.

The alpha(v)beta(3) integrin plays a pivotal role in angiogenesis and tumor metastasis. Angiogenic blood vessels overexpress alpha(v)beta(3) integrin, as in tumor neovascularization, and alpha(v)beta(3) integrin expression in other microvascular beds and organs is limited. Therefore, alpha(v)beta(3) integrin is a suitable receptor for tumor-targeting imaging and therapy. Recently, tetrameric and dimeric RGD peptides have been developed to enhance specificity to alpha(v)beta(3) integrin. In comparison to the corresponding monomeric peptide, however, these peptides show high levels of accumulation in kidney and liver. The purpose of this study is to evaluate tumor-targeting properties and the therapeutic potential of 111In- and 90Y-labeled monomeric RGD peptides in BALB/c nude mice with SKOV-3 human ovarian carcinoma tumors. DOTA-c(RGDfK) was labeled with 111In or 90Y and purified by HPLC. A biodistribution study and scintigraphic images revealed the specific uptake to alpha(v)beta(3) integrin and the rapid clearance from normal tissues. These peptides were renally excreted. At 10 min after injection of tracers, 111In-DOTA-c(RGDfK) and 90Y-DOTA-c(RGDfK) showed high uptake in tumors (7.3 +/- 0.6% ID/g and 4.6 +/- 0.8% ID/g, respectively) and gradually decreased over time (2.3 +/- 0.4% ID/g and 1.5 +/- 0.5% ID/g at 24 hr, respectively). High tumor-to-blood and -muscle ratios were obtained from these peptides. In radionuclide therapeutic study, multiple-dose administration of 90Y-DOTA-c(RGDfK) (3 x 11.1 MBq) suppressed tumor growth in comparison to the control group and a single-dose administration (11.1 MBq). Monomeric RGD peptides, 111In-DOTA-c(RGDfK) and (90)Y-DOTA-c(RGDfK), could be promising tracers for alpha(v)beta(3) integrin-targeting imaging and radiotherapy.

Thallium transport and the evaluation of olfactory nerve connectivity between the nasal cavity and olfactory bulb.

Little is known regarding how alkali metal ions are transported in the olfactory nerve following their intranasal administration. In this study, we show that an alkali metal ion, thallium is transported in the olfactory nerve fibers to the olfactory bulb in mice. The olfactory nerve fibers of mice were transected on both sides of the body under anesthesia. A double tracer solution (thallium-201, (201)Tl; manganese-54, (54)Mn) was administered into the nasal cavity the following day. Radioactivity in the olfactory bulb and nasal turbinate was analyzed with gamma spectrometry. Auto radiographic images were obtained from coronal slices of frozen heads of mice administered with (201)Tl or (54)Mn. The transection of the olfactory nerve fibers was confirmed with a neuronal tracer. The transport of intranasal administered (201)Tl/(54)Mn to the olfactory bulb was significantly reduced by the transection of olfactory nerve fibers. The olfactory nerve transection also significantly inhibited the accumulation of fluoro-ruby in the olfactory bulb. Findings indicate that thallium is transported by the olfactory nerve fibers to the olfactory bulb in mice. The assessment of thallium transport following head injury may provide a new diagnostic method for the evaluation of olfactory nerve injury.

Regional distributions of manganese, iron, copper, and zinc in the brains of 6-hydroxydopamine-induced parkinsonian rats.

Time courses of changes in manganese, iron, copper, and zinc concentrations were examined in regions of the brain of a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease using inductively coupled plasma mass spectrometry (ICP-MS). The concentrations were simultaneously determined in brain section at the level of the substantia nigra 1, 3, 7, 10, 14, and 21 days after the 6-OHDA treatment and compared with those of control rats. The distributions of these elements were obtained for 18 regions of the sagittal section (1-mm thick). The ICP-MS results indicated that Mn, Fe, Cu, and Zn levels of the 6-OHDA-induced parkinsonian brain were observed to increase in all regions that lay along the dopaminergic pathway. In the substantia nigra, the increase in Mn level occurred rapidly from 3 to 7 days and preceded those in the other elements, reaching a plateau in the 6-OHDA brain. Iron and Zn levels increased gradually until 7 days and then increased rapidly from 7 to 10 days. The increase in the copper level was slightly delayed. In other regions, such as the globus pallidus, putamen, and amygdala, the levels of Mn, Fe, Cu, and Zn increased with time after 6-OHDA treatment, although the time courses of their changes were region-specific. These findings contribute to our understanding of the roles of Mn and Fe in the induction of neurological symptoms and progressive loss of dopaminergic neurons in the development of Parkinson's disease. Manganese may hold the key to disturbing cellular Fe homeostasis and accelerating Fe levels, which play the most important role in the development of Parkinson's disease.

Axonal transport of rubidium and thallium in the olfactory nerve of mice.

Following intranasal administration of radioactive (86)Rb(+) and (201)Tl(+) in mice, we observed this direct transport via the olfactory nerve pathway. The (86)RbCl and (201)TlCl solutions were administered to two groups of mice, the unilateral intranasal and intravenous administration groups. After sacrifice, their heads were divided into the right and left side, which were then subdivided into seven parts; the nasal mucosa and brain regions were separated. Following the unilateral intranasal administration, uptake after 6 h by the olfactory bulb was significantly higher on the ipsilateral side ((86)Rb, 0.7 %dose; (201)Tl, 0.5 %dose) than on the contralateral side ((86)Rb, 0.08 %dose; (201)Tl, 0.15 %dose). Moreover, the (86)Rb and (201)Tl that accumulated in the olfactory bulb were gradually transported to other brain regions of the olfactory tract, the telencephalon and the diencephalon on the side corresponding to the nostril used for administration. Significant differences were observed between the right and left side of the brain regions 6 and 12 h after administration. Further, (201)Tl autoradiography clearly showed striped patterns of dense accumulation, localized in the region around the glomerular layer and granule cell layer of the olfactory bulb and around the olfactory cortex. These results provide clear evidence of axonal transport via the olfactory nerve pathway, from nasal cavity to the olfactory bulb, as well as to the olfactory cortex through the synaptic junctions. The olfactory transport of the (86)Rb(+) and (201)Tl(+) is thought to represent the behavior of K(+) in the olfactory system.

Multitracer screening: brain delivery of trace elements by eight different administration methods.

Trace elements are closely associated with the normal functioning of the brain. Therefore, it is important to determine how trace elements enter, accumulate, and are retained in the brain. Using the multitracer technique, which allows simultaneous tracing of many elements and comparison of their behavior under identical experimental conditions, we examined the influence of different administration methods, i.e., intravenous (IV), intraperitoneal (IP), intramuscular (IM), subcutaneous (SC), intracutaneous (IC), intranasal (IN), peroral (PO), and percutaneous (PC) administration, on the uptake of trace elements. A multitracer solution containing 16 radionuclides (i.e., 7Be, 46Sc, 48V, 51Cr, 54Mn, 59Fe, 56Co, 65Zn, 74As, 75Se, 83Rb, 85Sr, 88Y, 88Zr, 95mTc, and 103Ru) was used. The results indicated that the 83Rb brain uptake rate with intranasal administration was approximately twice those obtained with the other administration methods. This result indicated that a portion of Rb was delivered into the brain circumventing the blood circulation and that delivery could be accomplished mainly by olfactory transport. Multitracer screening of trace element delivery revealed differences in brain uptake pathways among administration methods.

227Th-EDTMP: a potential therapeutic agent for bone metastasis.

The biodistribution of 227Th-EDTMP and retention of its daughter nuclide 223Ra were examined. 227Th-EDTMP was found to show high uptake and long-term retention in bone. The clearance of 227Th-EDTMP from blood and soft tissues was rapid and the femur-to-tissue uptake ratios reached more than 100 within 30 min for all tissues except the kidney. Seven and 14 days after injection of 227Th-EDTMP, the retention index of 223Ra in bone showed high values, and the differences between these time points were not significant. Therefore, 227Th-EDTMP is a potential radiotherapeutic agent for bone metastasis.