Hypoxia as a factor for 67Ga accumulation in tumour cells.

Recent reports have demonstrated that hypoxia induces the up-regulation of transferrin receptor expression in tumour cells. Tumour cells take up 67Ga in the form of a 67Ga-transferrin complex via transferrin receptors. As a result, we attempted to determine the influence of hypoxic conditions on 67Ga uptake in tumour cells. B16 melanoma cells and LS180 colon cancer cells were incubated in 95% air/5% CO2 or 95% N2/5% CO2 for 1 h at 37 degrees C. Cellular uptake of 67Ga citrate was subsequently determined at 20, 40, 60 and 90 min. Uptake of the 67Ga-transferrin complex pre-chelated in vitro was similarly assessed. The effect of hypoxia on 67Ga binding to serum proteins was also investigated. Both B16 and LS180 cells displayed increased cellular uptake of 67Ga citrate in N2 gas in comparison to that in air (P < 0.0001). Hypoxia more prominently influenced cellular uptake of Ga-transferrin relative to that of 67Ga citrate (P < 0.0001). Hypoxia did not affect the percentages of 67Ga radioactivity bound to protein in medium supplemented with fetal calf serum, indicating that the results were not caused by the alteration of 67Ga-transferrin formation. These findings suggest the role of tissue hypoxia with respect to accumulation of 67Ga in tumours, which is likely mediated by transferrin receptors.

Differentiation of soft tissue haemangioma by 201Tl scintigraphy.

Radiological diagnosis of deep soft tissue is often difficult. In the present study, thallium-201 ( Tl) uptake into haemangiomas and deep malignant soft tissue tumours was investigated in order to assess its clinical utility. Tl scintigraphy was reviewed in four patients presenting with soft tissue haemangiomas. Early and delayed planar images, obtained at 15 min and 3 h following the intravenous injection of Tl (111 MBq), were examined. The Tl uptake ratio was calculated by dividing the count density of the tumour region of interest (ROI) by that of the background ROI. Results were compared with those of five cases of rhabdomyosarcoma and a single instance of angiosarcoma. All haemangioma lesions demonstrated increased Tl uptake in early images. However, Tl uptake in delayed images was markedly decreased. No significant differences were observed in the early uptake ratio between haemangiomas (1.60-2.72) and reference malignant tumours (1.48-2.45); however, the difference was significant in delayed images (range, 1.01-1.26 vs. 1.43-2.03, respectively) ( P<0.02). Deep soft tissue haemangiomas revealed Tl accumulation in early images; however, a rapid washout was observed in delayed images. This distinctive feature may facilitate the use of Tl scintigraphy in the diagnosis of haemangiomas.

Intense 201 Tl uptake in giant-cell tumour of bone.

The aim of this study was to determine the characteristics and clinical usefulness of 201Tl scintigraphy in giant-cell tumour of bone (GCT). Twenty-one patients with histopathologically proven benign GCT (22 lesions; 18 primary and four recurrent) underwent 201Tl scintigraphy. We also studied conventional osteosarcoma (10 lesions), a very common primary malignant bone tumour; and chordoma in the sacrum (four lesions), an entity requiring differential diagnosis from GCT of the sacrum. Early and delayed planar imaging was performed at 15 min (early) and 3 h (delayed) after the intravenous injection of 201Tl chloride (111 MBq). The Tl uptake ratio was calculated by dividing the count density of the tumour region of interest (ROI) by that of the background ROI. All GCT lesions showed increased Tl uptake in both early and delayed images. The mean Tl uptake ratios of primary GCT were 4.7 (range, 2.0-11.1) in the early images and 2.2 (range, 1.4-3.6) in the delayed images, and those of recurrent lesions were 5.8 (range, 2.4-11.5) in the early images and 2.7 (range, 2.0-4.3) in the delayed images. There were no significant differences between the uptake ratios in GCT and osteosarcoma, but the values of GCT tended to be higher than those of osteosarcoma, 3.1 (range, 1.7-4.4) in the early images and 1.8 (range, 1.3-2.3) in the delayed images. Chordoma did not show appreciable Tl uptake: the uptake ratio was 1.19 (range, 0.98-1.5) in the early images and 1.1 (range, 1.0-1.3) in the delayed images. In GCT, a benign lesion, Tl scintigraphy demonstrated marked uptake in both primary and recurrent lesions with no exceptions, precluding the use of Tl scintigraphy for the differential diagnosis of GCT from malignant tumours. However, the Tl scintigraphy can be used for excluding GCT when no lesional Tl uptake is observed, and diagnosing recurrent lesions on post-operative follow-up.

Anti-angiogenic therapy and radioimmunotherapy in colon cancer xenografts.

Angiogenesis is critical to the growth and metastatic process of malignant tumors. An endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), displays anti-angiogenic and anti-tumorigenic effects. The purpose of this investigation was to determine whether exogenously administered 2-ME would enhance the efficacy of radioimmunotherapy (RIT). Experimental RIT with 4.63 MBq of 131I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted in mice xenografted with LS 180 human colon cancer cells. 2-ME suspended in 0.5% carboxymethylcellulose was administered daily at a dose of 75 mg/kg per day. 2-ME administration suppressed tumor growth and improved the efficacy of RIT in comparison to RIT alone. Tumor volumes on day 13, expressed as a ratio relative to the initial volume, were 12.7 +/- 2.95 in the nontreated control, 4.73 +/- 0.89 with 2-ME, 3.05 +/- 0.37 with RIT and 0.97 +/- 0.20 with RIT+2-ME. Immunohistochemistry of tumor sections stained with an antibody against factor VIII demonstrated a decrease in microvessel number within tumors treated with 2-ME (7.9 +/- 0.8/200x field) as compared with that in control tumors (29.9 +/- 2.5). Cell proliferation assay at increasing concentrations of 2-ME showed direct cytotoxicity of 2-ME in vitro at 5 microM and greater. In conclusion, 2-ME enhanced the efficacy of RIT with 131I-A7 via inhibition of angiogenesis within the xenografts. The direct cytotoxicity of 2-ME appears to have contributed to this improvement. Anti-angiogenic therapy may prolong the dormancy of microscopic metastases while RIT may exterminate this population of cells. Therefore, the combined treatment may improve the therapeutic outcome of patients with disseminated cancer.

Assessment of left ventricular systolic and diastolic function based on the edge detection method with myocardial ECG-gated SPET.

The aim of this study was to determine the feasibility of assessing left ventricular systolic ejection and diastolic filling by the edge detection method with ECG-gated single-photon emission tomography (G-SPET) data. Fifty-two patients who had undergone both G-SPET and gated equilibrium blood pool scintigraphy (GBP) within an interval of 2 weeks were enrolled. For G-SPET, 740 MBq of technetium-99m methoxyisobutylisonitrile (MIBI) was injected at rest, and myocardial SPET was performed 60 min later using 360 degrees acquisition and 12 frames per cardiac cycle. In each frame, left ventricular volume was determined with automatic edge detection using a quantitative gated SPET program, and the time-volume curve was fitted by Fourier transform of the first to fourth harmonics. Ejection fraction (EF, %), peak ejection rate (PER, /s), peak filling rate (PFR, /s) and mean filling rate during the first third of diastolic time (1/3FRm, /s) were calculated from the fitted curve. These parameters were also calculated by means of GBP performed with 24 frames per cardiac cycle. Correlation coefficients in respect of EF, PER, PFR and 1/3FRm between G-SPET and GBP were 0.90 (P<0.001), 0.88 (P<0.001), 0.80 (P<0.001) and 0.82 (P<0.001), respectively. The correlations were good for EF, PER and 1/3FRm. Gated SPET dV/dt parameters were slightly lower compared with GBP values owing to the limited number of frames per cardiac cycle. It is concluded that left ventricular ejection and filling rates can be calculated using G-SPET with edge detection software, and in this study these parameters were significantly correlated with those derived using GBP. Diastolic abnormality on gated SPET study should be recognised as a positive finding, and appropriate gated SPET parameters should be further investigated.

(99m)Tc-sestamibi retention characteristics during pharmacologic hyperemia in human myocardium: comparison with coronary flow reserve measured by Doppler flowire.

UNLABELLED: The aim of the study was to investigate the increase in myocardial (99m)Tc-methoxyisobutylisonitrile (sestamibi) retention in humans during pharmacologic vasodilation. METHODS: For calculation of the increase in (99m)Tc-sestamibi retention during hyperemia, baseline and adenosine triphosphate (ATP)-induced hyperemic stress sestamibi studies were performed using a same-day rest-stress protocol. On the injection of sestamibi, left ventricular dynamic data were obtained for 90 s. The increase in sestamibi retention from baseline to hyperemia was calculated by the formula [abstract: see text] where Cm(h)(t) and Cm(b)(t) are myocardial counts on the tomographic image, and Cb(b)(tau) and Cb(h)(tau) are the left ventricular blood-pool counts during the first transit of sestamibi at baseline and during hyperemia, respectively. Coronary flow increase during intravenous ATP stress was measured using intracoronary Doppler flow guide wire and compared with the scintigraphic results of 28 measurements in 22 patients. RESULTS: Sestamibi retention increased as coronary flow velocity increased but plateaued at >2.5-3 times baseline flow velocity. The relationship between the increase in sestamibi retention (Y) and the increase in flow (X) is expressed as follows: Y = 0.44 + 0.60X - 0.068X(2) (r = 0.82). CONCLUSION: In humans, the increase in (99m)Tc-sestamibi myocardial retention underestimates coronary flow reserve, particularly at high flow rates. Knowledge of these tracer retention characteristics will contribute to a more comprehensive understanding of the manner and interpretation of stress sestamibi imaging.

Thymic lesions in patients with myasthenia gravis: characterization with thallium 201 scintigraphy.

PURPOSE: To assess thallium 201 ((201)Tl) single photon emission computed tomography (SPECT) for evaluation of thymic lesions associated with myasthenia gravis (MG), including lymphoid follicular hyperplasia (LFH) and thymoma. MATERIALS AND METHODS: (201)Tl SPECT and computed tomography (CT) were performed preoperatively in 46 patients with MG who had undergone thymectomy. SPECT was conducted 15 (early image) and 180 (delayed image) minutes after (201)Tl injection. Results were visually assessed, and (201)Tl uptake ratios (thymic lesion count density/lung count density) were measured for quantitative analysis. Uptake was analyzed among the normal thymus, LFH, and thymoma patient groups. RESULTS: Histopathologic results indicated a normal thymus, LFH, and thymoma in 19, 16, and 11 patients, respectively. Mean uptake ratios in the normal thymus, LFH, and thymoma were 0.96 (95% CI: 0.90, 1.03), 1.14 (95% CI: 1.04, 1.25), and 1.87 (95% CI: 1.56, 2.25), respectively, on early images and 1.09 (95% CI: 1.00, 1.18), 1.65 (95% CI: 1.48, 1.85), and 2.03 (95% CI: 1.65, 2.50), respectively, on delayed images. Thymoma showed more intense (201)Tl accumulation than did the normal thymus (P <.001) and LFH (P <.001) on early images. Both thymoma (P <.001) and LFH (P <.001) displayed more intense uptake than did the normal thymus on delayed images. CONCLUSION: (201)Tl SPECT can enable differentiation between normal thymus, LFH, and thymoma in patients with MG.

Experimental radioimmunotherapy with 186Re-MAG3-A7 anti-colorectal cancer monoclonal antibody: comparison with 131I-counterpart.

A murine IgG1 against a Mr 45 kD tumor-associated glycoprotein in human colorectal cancer, A7, was radiolabeled with 186Re by a chelating method with a mercaptoacetyltriglycine (MAG3). Its specific activity was 119 MBq/mg, which would be high enough for a therapeutic purpose, and its immunoreactivity was preserved well as was 131I-A7 labeled by the chloramine-T method. Growth of human colon cancer xenografts, 9.14 +/- 0.44 mm in diameter, in nude mice was significantly suppressed by an intravenous dose of 4.48 MBq of 186Re-A7. The therapeutic outcome with 186Re-A7 was better than that with 4.63 MBq of 131I-A7. Toxicity of treatments assessed by body weight change was similar with both conjugates. These results are likely caused by the tumor size and more favorable physical properties of 186Re than those of 131I.

Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment.

A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether this agent would enhance the response of tumours to experimental radioimmunotherapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of 131I-A7 anti-colorectal monoclonal antibody. A dose of 50 mg/kg of PTX was administered i.p. immediately after the 131I-A7 injection and daily thereafter for 7 days. The effect of PTX administration on 131I-A7 targeting in tumours was assessed with biodistribution and radioluminography on day 2. Intratumoural pO2 was measured with microelectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with 131I-A7 was significantly improved by PTX: tumour volumes on day 15, relative to the initial volume, were 16.8+/-3.60 in the nontreated controls, 13.9+/-2.17 with PTX, 3.43+/-0.44 with RIT, and 1.86+/-0.59 with RIT+PTX (P<0.05). PTX administration did not alter the biodistribution or intratumoural distribution of 131I-A7. However, intratumoural pO2 was significantly improved by PTX administration: 16.9+/-9.75 mmHg in control tumours versus 25.6+/-11.3 mmHg in PTX-treated tumours (P<0.01). These results indicate that PTX-induced radiosensitisation of tumour cells due to better oxygenation is responsible for the better RIT outcomes, because the net radiation absorbed dose to the tumours did not appear to be changed.

Methylxanthine sensitization of human colon cancer cells to 186Re-labeled monoclonal antibody.

UNLABELLED: Tumor cells lacking the functional p53 suppressor gene may arrest at the G2 phase of the cell cycle after exposure to ionizing radiation, resulting in increased radioresistance. Methylxanthines (MTXs), such as pentoxifylline (PTX) or caffeine (CAF), can inhibit the G2-phase checkpoint arrest of damaged cells and thus radiosensitize them. However, the effect of MTX in cells irradiated with low-dose-rate beta-emission is not well understood. METHODS: A clonogenic assay was performed with LS180 human colon cancer cells lacking the functional p53 suppressor gene. Cells were irradiated with increasing concentrations of 186Re-mercaptoacetyltriglycine (186Re-MAG3)-labeled A7 monoclonal antibody against colorectal cancer (0-925 kBq/mL) at 37 degrees C in 5% CO2 for 24 h in the presence or absence of PTX (0-2 mmol/L) or CAF (0-5 mmol/L). The enhancement ratio (ER) with MTX was calculated as a ratio of 50% cell-killing concentration of 186Re-MAG3-A7 in control cells to that in cells treated with PTX or CAF. The cell cycle distribution was analyzed with a flow cytometer. RESULTS: The concentration of 50% cell kill was 474 kBq/mL 186Re-MAG3-A7. Both PTX and CAF dose dependently enhanced the cytotoxicity of 186Re-MAG3-A7: ERs of 0.5 mmol/L PTX, 2 mmol/L PTX, 1 mmol/L CAF, and 5 mmol/L CAF were 1.50, 2.18, 1.54, and 2.63, respectively. Flow cytometry showed that the percentage nonirradiated cells in the G2/M phase of the cell cycle was 11.3% +/- 1.66%. On the other hand, cells exposed to 186Re-MAG3-A7 accumulated in the G2/M phase of the cell cycle (40.2% +/- 1.46%), which was inhibited by the presence of 1 mmol/L PTX (19.8% +/- 8.12%) or 2 mmol/L CAF (26.9% +/- 6.21%). CONCLUSION: Cellular modulation of the cell cycle with PTX and CAF radiosensitized LS180 colon cancer cells exposed to 186Re radiation.

Technetium-99m-tetrofosmin would be a substrate for multidrug resistance-associated protein (MRP): comparison between a leukemia cell line with high MRP gene expression and its parental cell line.

UNLABELLED: The kinetics of cellular accumulation and retention of technetium-99m-tetrofosmin (99mTc-TF) were investigated in wild type HL60/WT cell line and in its doxorubicin-resistant HL60/DOX cell line with multidrug resistance-associated protein (MRP), but without P-gp overexpression, to determine whether 99mTc-TF is a substrate for MRP. METHODS: The accumulation and washout of 99mTc-TF were observed in both cell lines at 37 degrees C. The effect of verapamil on the kinetics was also assessed. RESULTS: 99mTc-TF net accumulation was significantly lower in HL60/DOX (1.35 +/- 0.23%) than in HL60/WT (12.79 +/- 0.47%) at 60 min (P < 0.001). Three minutes after exchanging the incubation solution to the tracer-free medium, only 18.20 +/- 0.34% of 99mTc-TF remained in HL60/DOX, whereas 84.74 +/- 0.65% did in HL60/WT (P < 0.001). In the presence of 10 microM verapamil, 99mTc-TF net accumulation in HL60/DOX was 302% of the control and the washout was significantly delayed. CONCLUSION: 99mTc-TF would be a substrate for MRP and 99mTc-TF may be used as a functional imaging agent of MRP in vivo.

Optimal timing of administration of hyperthermia in combined radioimmunotherapy.

Local hyperthermia (HT) may enhance the efficacy of radioimmunotherapy (RIT). However, the optimal timing of HT relative to administration of antibody is unknown. Human colon cancer xenografts (290 +/- 26 mm3) were treated with 4.63 MBq 131I-A7 monoclonal antibody (MAb) anti-Mr 45,000 glycoprotein antigen on colorectal cancer, and HT at 43 degrees C for 1 h was administered at: (A), 2 days after the 131I-A7 injection at the maximum 131I-A7 tumor accumulation (radiation); (B), soon after the 131I-A7 injection aiming to increase the tumor accumulation of 131I-A7 due to HT vascular effects; or (C), 2 days before the 131I-A7 injection in an attempt at injecting 131I-A7 when increased antigen expression could be expected. Specific growth delay (SGD) of tumors was calculated as (Tqtreat-Tqcontrol)/Tqcontrol where Tq was tumor quadrupling time. The biodistribution and intratumoral distribution of 131I-A7 were investigated to explore the mechanism of tumor response among the different HT regimens. HT alone produced some antitumor effect (SGD 1.90 +/- 0.26), which was less effective than RIT (3.11 +/- 0.50). HT soon after 131I-A7 RIT (B) significantly enhanced RIT efficacy (6.57 +/- 0.51, p < 0.0001) whereas neither HT at 2 days after RIT (A) nor at 2 days before RIT (C) did so. Biodistribution study revealed that HT soon after RIT (B) increased the tumor radiation absorbed dose by a factor of 2.4, while HT after RIT (A) did not increase radiation dose and HT before RIT (C) decreased it. Radioluminograms of tumor sections indicated that HT soon after RIT (B) improved the uniformity of 131I-A7 distribution whereas HT after RIT (A) did not and HT before RIT (C) diminished the uniformity of A7 distribution. In conclusion, the best therapeutic efficacy was obtained when HT was combined soon after the initiation of RIT with 131I-A7. The increased tumor radiation absorbed dose and the uniform intratumoral distribution of 131I-A7 were important factors underlying this improvement, and the additive cytotoxicity of HT is suspected to some extent. HT-induced radiosensitization of tumor was not apparent in this model when HT was given 2 days after 131I-A7 MAb.

Assessment of improvement of myocardial fatty acid uptake and function after revascularization using iodine-123-BMIPP.

UNLABELLED: We used beta-methyl iodophenyl pentadecanoic acid (BMIPP) to evaluate changes in myocardial fatty acid utilization before and after revascularization and the ability of BMIPP to predict functional recovery in patients with chronic coronary artery disease. METHODS: Thirty-four patients with chronic coronary artery disease (60 +/- 10 yr) underwent BMIPP and 201Tl SPECT (stress-reinjection 201Tl in 29 patients and resting 201Tl in 5 patients) before and 2-5 wk after percutaneous transluminal angioplasty (n = 23) or coronary artery bypass surgery (n = 11). Cardiac function was evaluated by gated blood-pool scintigraphy (n = 26) or two-dimensional echocardiography (n = 8) before and after revascularization. RESULTS: In 32 patients with reduced BMIPP uptake before revascularization, scintigraphic findings with 201Tl improved in 28 patients after revascularization. In these 28 patients, BMIPP uptake improved in 20 patients (71%). Wall motion abnormality was observed in 16 of these 20 patients before revascularization, with 15 showing wall motion improvement after revascularization. In eight patients without improvement of BMIPP uptake, despite 201Tl uptake improvement, wall motion abnormality was observed in four patients before revascularization; after revascularization, one showed wall motion recovery, and three did not. Ejection fraction (EF) improvement after revascularization correlated best with the area of improved BMIPP uptake (r = 0.84, p < 0.0005). EF improvement also correlated with the area of improved reinjection 201Tl uptake (r = 0.54, p < 0.05) and improved 201Tl uptake at stress after revascularization (r = 0.48, p < 0.05). The area of discordant uptake of BMIPP less than reinjection 201Tl uptake before revascularization was a good predictor of EF improvement after revascularization (r = 0.58, p < 0.01); however, the area of reversible 201Tl defect was not (r = 0.34, p = 0.15). CONCLUSION: In patients with chronic coronary artery disease, functional improvement after revascularization is closely related to the recovery of BMIPP uptake. Discordant BMIPP uptake less than reinjection 201Tl uptake is a potential predictor of functional recovery.

Absent myocardial I-123 BMIPP uptake in a family.

A 72-year-old woman with hypertension showed no sign of myocardial accumulation of 123I-BMIPP, and 201Tl and 123I-MIBG scintigraphy demonstrated normal findings. Electrocardiography showed left axis deviation with inverted T waves in leads I, aVL, V2-6 and QT prolongation. Coronary arteriography, two dimensional echo cardiography and laboratory data showed no abnormality. Her 66-year-old sister with non-insulin-dependent diabetes mellitus also had no myocardial BMIPP uptake, but had normal 201Tl finding. ECG and chest film findings were normal. Laboratory data indicated slightly high fasted blood glucose, triglyceride and total cholesterol. Four sons of a 72-year-old woman also underwent BMIPP scintigraphy. No BMIPP uptake was also observed in her 2nd son (49 years old) and his electrocardiogram showed QT prolongation. Since these rare findings indicating no myocardial BMIPP uptake were seen in a family, we suspected that a hereditary myocardial metabolic abnormality accounted for them.

Myocardial scintigraphic study with 123I 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid in patients with hypertrophic cardiomyopathy.

123I 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) myocardial scintigraphy and exercise stress thallium (TI)-201 myocardial scintigraphy were performed in 17 patients with hypertrophic cardiomyopathy (HCM) to evaluate the existence of abnormal fatty acid metabolism in the myocardium and the relationship between this abnormality and myocardial ischemia. On the BMIPP scintigraphy, abnormalities were found in 12 of 17 patients (71%). Five patients showing no abnormalities on the BMIPP scintigraphy had well preserved exercise tolerance and had longer exercise duration than the others showing BMIPP scintigraphic abnormalities (P < 0.001). On the evaluation of the segmental abnormalities, TI scintigraphic abnormalities were found in 15 (50%) of 30 segments showing decreased accumulation of BMIPP. On the other hand, BMIPP scintigraphic abnormalities were found in all segments showing decreased accumulation of TI. The sites of decreased accumulation of BMIPP and TI were in good agreement with the sites of wall hypertrophy. Four patients showing BMIPP scintigraphic abnormalities and no T1 scintigraphic abnormalities were in higher New York Heart Association functional classes, had shorter exercise duration (P < 0.05) than the 5 patients showing no abnormalities on either scintigraphy. It is concluded that abnormalities of fatty acid metabolism in the heart are detected at a high rate in patients with HCM, and may be due in part to factors other than myocardial perfusion disturbance.

Impairment of regional fatty acid uptake in relation to wall motion and thallium-201 uptake in ischaemic but viable myocardium: assessment with iodine-123-labelled beta-methyl-branched fatty acid.

In coronary artery disease, discrepancy in the uptake of thallium-201 and of methyl-branched fatty acid at rest has been described. The purpose of this study was to evaluate iodine-123 labelled beta-methyl-branched fatty acid (BMIPP) myocardial uptake and wall motion at rest in segments with stress-induced ischaemia identified by stress 201Tl tomography in patients with chronic coronary artery disease. 123I-BMIPP myocardial tomography was performed at rest and was compared with the findings of exercise-reinjection 201Tl tomography in 45 patients with chronic coronary artery disease. Regional wall motion was evaluated by contrast left ventriculography in 36 patients. Among 237 segments with reversible 201Tl defects, equally decreased uptake on both reinjection 201Tl and BMIPP images was observed in 93 (39%), more severely decreased uptake of BMIPP in 118 (50%) and more severely decreased uptake of reinjection 201Tl in 26 (11%). On the other hand, among 90 segments with non-reversible 201Tl defects, each pattern was observed in 71 (79%), 6 (7%) and 13 (14%) segments, respectively. When comparing the ischaemic segments with and without more severely reduced uptake of BMIPP than of reinjection 201Tl, wall motion was impaired to a greater extent in the segments with more severely reduced uptake of BMIPP than of reinjection 201Tl [severe hypo- or dyskinesis was present in 64 (70%) of 91 segments and in 24 (22%) of 110 segments, respectively, P<0.005]. In patients with chronic coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection 201Tl in the segments with stress-induced ischaemia, while in most of the fixed perfusion defects BMIPP and reinjection 201Tl uptake decreased concordantly. In ischaemic myocardium, wall motion was impaired to a greater extent in those segments which showed more severely reduced uptake of BMIPP than of reinjection 201Tl. In ischaemic but viable myocardium, discordant BMIPP uptake less than reinjection 201Tl uptake may indicate metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities. In conclusion, the combination of resting BMIPP and stress-reinjection 201Tl imaging may provide information on metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities.

[Value of 123I-BMIPP scintigraphy in patients with ischemic heart disease: comparison with exercise 201Tl SPECT].

To evaluate 123I labeled beta-methyl-branched fatty acid (BMIPP) myocardial uptake at rest in the segment with and without stress induced ischemia in patients with coronary artery disease, 123I-beta-methyl-branched fatty acid myocardial scintigraphy was performed at rest and was compared with the findings of stress-reinjection 201Tl myocardial scintigraphy in 31 patients with coronary artery disease. In 159 ischemic myocardial segments, equally decreased uptake on both reinjection 201Tl and fatty acid images was observed in 64 segments, more severely decreased uptake of fatty acid in 76 segments, and more severely decreased uptake of reinjection thallium in 19 segments. On the other hand, in 53 non-reversible defects, each patterns was observed in 41, 3, and 9 segments respectively. When comparing the ischemic segments with more reduced uptake of fatty acid than reinjection thallium (Group 1) and the ischemic segments with equally or less reduced fatty acid uptake than reinjection thallium (Group 2), wall motion was more severely impaired in Group 1 than in Group 2 (severe hypo- to dyskinesis was present in 32 of 54 segments in group 1 and in 21 of 75 segments in group 2, p < 0.005). In conclusion, in patients with coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection 201Tl in the segments with stress induced ischemia and wall motion was more impaired in these segments. BMIPP myocardial imaging may provide information on metabolic alterations at rest independent of perfusion abnormalities in patients with coronary artery disease.

Twenty-four-hour quantitative thallium imaging for predicting beneficial revascularization.

To determine the utility of 24-h thallium single-photon emission tomographic imaging for the assessment of myocardial viability, 40 patients with persistently decreased uptake on 3-h delayed imaging after exercise were studied before and after bypass surgery (n = 34) or coronary angioplasty (n = 6). Wall motion improvement after revascularization was also analysed in 23 patients with respect to the segments with and without 24-h redistribution. Of a total of 113 segments without redistribution at 3-h imaging after exercise, 62 (55%) demonstrated redistribution at 24 h. After revascularization 57 (92%) of these 62 segments revealed improvement of thallium uptake. On the other hand 40 (78%) of the 51 segments with persistently decreased thallium uptake until 24 h did not show improvement of uptake after revascularization. Of the 15 segments with > 50% relative thallium uptake and without redistribution on 24-h images, ten showed improvement of thallium uptake after revascularization. Hence higher uptake even without 24-h redistribution may indicate viability. Regional wall motion improved in 22 of 23 segments with redistribution on 24-h images, and did not improve after revascularization in 19 of 22 segments without redistribution at 24 h. These data suggest that 24-h late imaging with quantitative analysis may provide reliable information about reversible myocardial ischaemia in segments that demonstrate a fixed perfusion abnormality on conventional 3-h delayed imaging.

[Nuclear cardiology with new radiopharmaceuticals].

In the field of nuclear cardiology, 99mTc labeled myocardial perfusion agents such as MIBI, Tetrofosmin and Teboroxime, 111In-antimyosin for imaging of myocardial necrosis, 123I-betamethyl-iodophenylpentadecanoic acid (BMIPP) for imaging of myocardial fatty acid metabolism and 123I-metaiodobenzylguanidine (MIBG) for imaging of myocardial adrenergic function are introduced recently in Japan. Improved image quality and simultaneous evaluation of myocardial perfusion, function and wall motion can be obtained with use of 99mTc labeled myocardial perfusion agents. 111In-antimyosin enables specific imaging of myocardial necrosis which leads to the use for wide variety of heart diseases. Discrepancy of the myocardial perfusion and metabolism in case of stunned myocardium or cardiomyopathy can be evaluated by 123I-BMIPP in conjunction with perfusion agent. Recently wide variety of diseases which may have cardiac adrenergic abnormality are targeted for 123I-MIBG imaging. These new radiopharmaceuticals are expected to be powerful tool for evaluation of the pathophysiology including severity and prognosis and evaluation of the etiology of the various heart diseases.