Noriyuki Shuke

A quantitative approach to technetium-99m hexamethylpropylene amine oxime.

A non-invasive, simple method for the quantitative evaluation of brain perfusion is presented using intravenous radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). Graphical analysis was employed for the evaluation of the unidirectional influx constant (ku of the tracer from the blood to the brain. The ku values were standardized to provide objective and comparable values, brain perfusion indices (BPI), among studied subjects by setting the ratio of ROIbrain size to ROIaorta size at 10. The wholebrain BPI values for the normal control subjects showed a significant negative correlation with advancing age (r = -0.632, P =0.0204, n =13). The mean of the wholebrain BPI of 7.0 (SD =1.4) in 20 patients with cerebrovascular disorders was significantly lower than that of 10.6 (SD =1.5) in 13 normal control subjects. The BPI measurements showed only minimal intra- and interobserver variability. Changes of the ratio of ROIaorta size and ROIbmin size did not significantly influence the BPI values. Hemispherical BPI values in 19 subjects (n =38) showed highly significant correlations with the hemispherical mean cerebral blood flow values obtained from Xenon-133 single photon emission tomography (SPET) (r =0.926, P =0.0001 for the early picture method and r =0.932, P =0.0001 for the sequential picture method). This technique is easy to apply as an adjunct to SPET and may be helpful in the quantitative evaluation of brain perfusion in routine clinical studies.

Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylprophylene amine oxime

The previously reported method for quantitative measurements of whole-brain or hemispheric-brain perfusion using technetium-99m hexamethylpropylene amine oxime (HMPAO) radionuclide angiography is now further developed so that regional cerebral blood flow (rCBF) can be measured. Lassens correction algorithm is used for the linearization of a curve-linear relationship between the radioactivity in the brain and blood flow as seen with single-photon emission tomography (SPET) images. In this algorithm, the cerebral hemisphere was chosen as the reference region and the correction factor α was adapted to rCBF in the reference region. This new method of measuring CBF from SPET has been validated in 33 normal subjects and 22 patients with cerebrovascular disease. Regional CBF values in 20 brain regions of the normal subjects were in good agreement with reported values measured by other methods. Regional CBF in the frontal cortex was greater than that in the temporal, parietal or occipital cortex for the entire age range. This hyperfrontal perfusion tended to be less pronounced with advancing age. Seventeen patients with unilateral brain infarction showed significantly lower rCBF than normal subjects. The infarct core showed a low rCBF value of 11.1 ml/ 100 g/min on average. An increase in rCBF after acetazolamide administration was observed and mesured with this method in five patients with unilateral occlusive vascular pathology. These results suggest that this non-invasive method (without any blood sampling) permits the routine measurement of rCBF from HMPAO SPET tomograms of blood flow.

Visualization of the thymus with therapeutic doses of radioiodine in patients with thyroid cancer

Two cases of papillary carcinoma of the thyroid are presented in which whole-body scans following therapeutic doses of iodine-131 revealed intense anterior mediastinal uptake. In both cases, the mediastinal uptake was absent from scans obtained after removal of the entire thymus. Histologically, the resected thymus glands showed hyperplasia and contained neither thyroid tissue nor metastatic foci of thyroid carcinoma. We therefore concluded that anterior mediastinal uptake of radioiodine may be caused by hyperplasia of the thymus.

Scintigraphic evaluation of pamidronate and corticosteroid therapy in a patient with progressive diaphyseal dysplasia (Camurati-Engelmann disease)

A 27-year-old woman with progressive diaphyseal dysplasia (Camurati-Engelmann disease) received pamidronate and corticosteroid therapy for bone pain. During therapy, disease activity was assessed serially using bone scintigraphy with Tc-99m HMDP. With pamidronate administration, the bone pain became worse and diaphyseal uptake of Tc-99m HMDP increased, whereas corticosteroid administration improved the bone pain and reduced the diaphyseal uptake. In this case, pamidronate and corticosteroid produced different effects. Bone scintigraphy allowed an objective assessment of the response to these treatments, accurately reflecting clinical symptoms.

Evaluation of suspected malignant pulmonary lesions with 201Tl single photon emission computed tomography.

201Tl single photon emission computed tomography (SPECT) was evaluated in 170 patients suspected of having a malignant pulmonary lesion greater than 20 mm in diameter on the surgical specimen. Delayed SPECT (at 3 h after injection) visualized all of the 147 malignant pulmonary lesions and 16 of the 23 (69.6%) benign pulmonary lesions, and generally exhibited the lesion more clearly than the early SPECT images (at 15 min after injection). There was no significant difference in delayed ratio (uptake ratio of the lesion to the normal lung on delayed scan) among the various histological groups except between the adenocarcinoma and large cell carcinoma groups (P < 0.05), and no difference was noted between the malignant and benign lesions. However, in retention index (degree of retention in the lesion) a significant difference was noted between the malignant and benign lesions (P < 0.01), although there was no significant difference in this index among malignant different histology groups. These results indicate that this method is useful for visualizing malignant pulmonary lesions greater than 20 mm in diameter to exclude the possibility of malignancy in the lesions when no abnormal 201Tl accumulation is observed. When the lesion shows abnormal 201Tl accumulation, the retention index seems to help differentiate malignant from benign lesions.

Evaluation of normal fatty replacement of the thymus with chemical‐shift MR imaging for identification of the normal thymus

To clarify the influences of age and gender on normal fatty replacement of the thymus in childhood, adolescence, and early adulthood using chemical‐shift MRI.

Efficacy, toxicity and mode of interaction of combination radioimmunotherapy with 5-fluorouracil in colon cancer xenografts

Purpose:The feasibility of radioimmunotherapy (RAIT) combined with 5-fluorouracil (5-FU) was examined in colon cancer xenografts. The mode of interaction of the two treatments was also investigated. Methods: Mice bearing human colon cancer were treated with a combination of 4.63 MBq (L-RAIT) or 9.25 MBq (H-RAIT) 131I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg−1 day−1 for 5 days. Myelotoxicity was monitored by blood cell counts and intestinal toxicity was assessed by the dosimetry. The results were compared with those of a single-modality therapy. Results: The combination of 5-FU with H-RAIT enhanced the antitumor effect, improving the tumor quadrupling time from 25.3 ± 9.59 days to 31.3 ± 8.32 days (P < 0.05) and inducing tumor regression in 7 out of 10 mice, compared to 3 out of 9 mice treated with H-RAIT alone. The efficacy of L-RAIT was also improved by the combination. Analysis of the dose/response relationship showed an additive interaction of the two modalities. The combination of 5-FU with RAIT induced slightly more severe myelotoxicity than a single-modality treatment, but blood cell counts recovered similarly. Dose estimation suggested that RAIT does not increase the intestinal toxicity of 5-FU. Conclusion: The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.

Intraperitoneal radioimmunotherapy in treating peritoneal carcinomatosis of colon cancer in mice compared with systemic radioimmunotherapy

Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current investigation, the efficacy of radioimmunotherapy (RIT) with i.p. administration of an anti‐colorectal cancer IgG1,131I‐A7, was compared to that with i.v. administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131I‐A7 and i.p. administered irrelevant 131I‐HPMS‐1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long‐term survival: untreated mice (n=11), mice undergoing i.p. RIT with 131I‐A7 (n=11), mice undergoing i.v. RIT with 131I‐A7 (n=11) and mice undergoing non‐specific i.p. RIT with 131I‐HPMS‐1 (n=5). Intraperitoneal injection of 131I‐A7 produced faster and greater tumor accumulation than i.v. injection: 34.2±16.5% of the injected dose per g (% ID/ g) and 11.1±3.6% ID/g at 2 h, respectively (P<0.0001). Consequently, cumulative radioactivity in tumors was 1.73‐fold higher with i.p. injection. 131I‐HPMS‐1 did not show specific accumulation. Non‐specific RIT with 131I‐HPMS‐1 (mean survival, 26.0±2.5 days) did not affect the survival as compared to no treatment (26.7±1.9 days). Intravenous RIT with 131I‐A7 prolonged the survival of mice to 32.8±1.8 days (P<0.01). Intraperitoneal RIT with 131I‐A7 improved the survival more significantly and attained cure in 2 of 11 mice (P<0.05 vs. i.v. RIT). In conclusion, i.p. RIT is more beneficial in treating peritoneal carcinomatosis of colon cancer than i.v. RIT in a murine model.

Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by 123 I-BMIPP SPECT and 99m Tc-tetrofosmin electrocardiographically gated SPECT

Objective: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).Methods: Thirty-nine patients with cardiomyopathies (58±14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis.Results: BMIPP uptake was decreased (p<0.05), and its washout was increased (p<0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p>0.05), but showed a significant correlation with H/M-TF (p<0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p<0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p>0.05) but had a significant correlation with regional perfusion (p<0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p<0.005) and perfusion (p<0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively.Conclusion: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.

Statistical parametric mapping in brain single photon computed emission tomography after carbon monoxide intoxication.

The purpose of this retrospective study was to assess regional cerebral blood flow in patients after carbon monoxide intoxication by using brain single photon emission computed tomography and statistical parametric mapping. Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms after carbon monoxide intoxication were studied with brain single photon emission tomography imaging with 99mTc-hexamethyl-propyleneamine oxime. Forty-four control subjects were also studied. We used the adjusted regional cerebral blood flow images in relative flow distribution (normalization of global cerebral blood flow for each subject to 50 ml.100 g−1.min−1 with proportional scaling) to compare these groups with statistical parametric mapping. Using this technique, significantly decreased regional cerebral blood flow was noted extensively in the bilateral frontal lobes as well as the bilateral insula and a part of the right temporal lobe in the patients with delayed neuropsychiatric sequelae as compared with normal volunteers (P< 0.005). In the patients with no neuropsychiatric symptoms, significantly decreased regional blood flow in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased regional cerebral blood flow in the right frontal lobe and insula in the patients with delayed neuropsychiatric sequelae as compared to those with no neuropsychiatric sequelae. It is concluded that statistical parametric mapping is a useful technique for highlighting differences in regional cerebral blood flow in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced blood flow noted in this investigation supports the contention that the decrease following carbon monoxide intoxication may be prolonged and further worsen in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.