Intraperitoneal radioimmunotherapy to treat the early phase of peritoneal dissemination of human colon cancer cells in a murine model.

BACKGROUND AND AIM: In patients with a high risk of peritoneal dissemination of colon cancer, a treatment adjuvant to surgical resection would improve their prognosis. We aimed to determine whether radioimmunotherapy employing radiolabelled monoclonal antibody would work in this situation. METHODS: A murine model of peritoneal dissemination was established in female Balb/c nu/nu mice by intraperitoneal injection of LS180 human colon cancer cells. Radioimmunotherapy with 7.4 MBq of a murine IgG1, anti-colorectal A7 monoclonal antibody, radiolabelled with (131)I by the chloramine-T method was conducted intraperitoneally on days 0, 3, 7 and 14 after cell inoculation, respectively. RESULTS: Radioimmunotherapy at any timing improved survival of mice as compared with those of non-treated mice and mice treated with a daily dose of 30 mg x kg(-1) of 5-fluorouracil for 4 consecutive days. The best improvement was obtained when radioimmunotherapy was conducted on day 0. CONCLUSION: These results indicate that intraperitoneal radioimmunotherapy may effectively kill colon cancer cells disseminated in the peritoneal cavity before formation of tumours and, therefore, may work as an adjuvant treatment to prevent peritoneal metastasis of colon cancer.

Binding with serum components favorably affects cellular uptake of 111In-oligonucleotide in a leukemia cell line.

PURPOSE: The influence of serum components on the intracellular uptake of an 111In-oligonucleotide (ODN) against mdr1 mRNA was investigated in the murine leukemia cell line, P388/S, and its mdr1-overexpressed P388/R. METHODS: 111In-ODNs naked and vectorized with lipids were analyzed for binding with serum components using high-performance liquid chromatography (HPLC). 111In-ODN was incubated in albumin and transferrin solutions. 111In-DTPA and 111In-mononucleotide were incubated in serum. Degradation of naked 111In-ODN was detected in phosphate buffered saline (PBS) and serum containing endonuclease S1. Cellular uptakes of naked and vectorized 111In-ODN in the above cells were examined with and without fetal calf serum (FCS). RESULTS: Time-dependent binding of naked and vectorized 111In- ODN with serum components was observed throughout 24 hours. Transchelation of 111In to transferrin was not detected. HPLC profiles of 111In-DTPA and 111In-mononucleotide did not change in serum. Degradation of 111In-ODN by S1 was less remarkable in serum than in PBS. Specific accumulation of vectorized 111In-ODN in P388/R cells was achieved in culture with and without 10% FCS. CONCLUSIONS: This study verified the intense binding of ODN with serum components, leading to no inhibition on ODN intracellular specific uptake. Binding with serum components protects 111In-ODN from degradation by endonuclease and thus may facilitate ODN transmembrane delivery.

Respiratory distress caused by radioiodine therapy in patients with differentiated thyroid cancer.

Respiratory distress accompanied by stridor is an uncommon complication of 131I radioiodine therapy for differentiated thyroid cancer that occurs within 48 hours of treatment. This report presents three cases with papillary thyroid carcinoma in which 131I therapy caused this acute complication. One of them had no apparent risk for this complication such as the existence of remnant thyroid tissue or laryngeal problems before the treatment. These cases remind physicians that 131I therapy is not a simple, riskless procedure.

Fluctuation of adenosine concentration by modes of intravenous infusion based on mathematical simulation and experiments.

OBJECTIVE: Adenosine, which has been used for a myocardial perfusion scan, shows rapid clearance from blood because of its short half-life of <10 seconds. This simulation study evaluates influences of modes of radionuclide injection on ventricular adenosine concentration when one intravenous injection line is used. METHODS: Assuming that radionuclide injection is a unit impulse, time-activity curves were measured in the left ventricle (LV) and fitted by a gamma function. Typical patterns of concentration fluctuation when adenosine infusion was temporarily modified were calculated by the convolution integral of input function and unit impulse response. Variation of concentration was measured by experiments using continuous 99mTc injection and co-infusion of water via a three-way stopcock. Modes of co-infusion with various infusion speeds and volumes were examined. RESULTS: Intermission of adenosine infusion and rapid displacement by radionuclide co-injection significantly influenced the adenosine concentration in LV. Intermission of adenosine infusion for 2 seconds caused a 15% decrease in the adenosine concentration in the left ventricle. When a square-shaped input was assumed, a three-fold higher concentration of adenosine for 3 seconds created by radionuclide injection resulted in a +42% increase in the LV concentration. Based on a measured input function, radionuclide injection using three-way stopcock through one route caused a two- to three-fold increase in the steady concentration in the vein just after injection. When 0.5 ml of radionuclide was slowly co-injected, with three ways opened, it caused a relatively low fluctuation, creating a +34% to -47% change in concentration of LV. A flush of radionuclide with physiological saline significantly increased the adenosine concentration in LV, when short half-lives were assumed. CONCLUSION: An intravenous adenosine and radiopharmaceutical injection in the same line is feasible. However, the fluctuation of concentration depends significantly on the mode of injection. To minimize the fluctuation, a slow injection of a small volume of a myocardial imaging agent via a co-injection route, with three ways opened, is recommended.

99mTc-sestamibi to monitor treatment with antisense oligodeoxynucleotide complementary to MRP mRNA in human breast cancer cells.

OBJECTIVE: Technetium-99m sestamibi (MIBI) has been utilized to evaluate multi-drug resistance (MDR) phenomenon of malignant tumors and to predict chemotherapeutic effects on them. The current investigation examined the possibility of monitoring changes with respect to mRNA expression of multi-drug resistance associated protein (MRP) following antisense oligodeoxynucleotide (AS-ODN) treatment involving 99mTc-MIBI. METHODS: The human breast cancer MCF-7 cell line and its MDR-induced MCF-7/VP cell line were employed. Cell suspensions of the two cell lines at 1 x 10(4) cells/ml were inoculated in 24-well plates (0.2 ml/well) and incubated for one day. Antisense (AS) 20-mer phosphorothioate ODN complementary to the coding region of MRP mRNA and its sense (S) ODN were administered at final concentrations up to 25 microM, followed by a 5-day incubation. 99mTc-MIBI solution was added to each well and incubated for 30 min. Cellular 99mTc-MIBI uptake was corrected for protein concentration. MRP mRNA expression levels were analyzed via the reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Cellular uptake of 99mTc-MIBI in MCF-7/VP cells was only 15% of that of MCF-7 cells. Following AS-ODN treatment at 25 microM for five days, 99mTc-MIBI uptake in MCF-7/VP cells increased 2.4-fold in comparison with non-treated control cells. 99mTc-MIBI uptake in MCF-7 cells was unaffected by AS-ODN administration. Sense ODN did not alter uptake in either cell line. RT-PCR confirmed reduction of MRP mRNA in MCF-7/VP cells following AS-ODN treatment. CONCLUSION: Effects of AS-ODN administration on MRP function can be monitored via assessment of cellular uptake of 99mTc-MIBI.

Effect of left ventricular function on diagnostic accuracy of FDG SPECT.

OBJECTIVES: Fluorine-18 fluorodeoxyglucose (FDG) SPECT has emerged as an alternative to dedicated PET imaging. However, it remains uncertain whether FDG SPECT is an as accurate for viability assessment as FDG PET in patients with severely reduced left ventricular function. The aim of the study was to assess the diagnostic accuracy of FDG SPECT in a head-to-head comparison with FDG PET, and divide the patients according to the severity of left ventricular dysfunction. METHODS: A total of 47 patients, with a history of myocardial infarction underwent FDG/perfusion (99mTc-sestamibi or 201Tl) SPECT as well as FDG/13N-ammonia PET. The patients were divided into 2 subgroups based on the left ventricular ejection fraction (LVEF) (35% cutoff). The left ventricular myocardium was divided into 13 segments, and each segment was classified as viable or scar using a semi-quantitative scoring system based on defect severity and the presence or absence of perfusion-FDG mismatch. RESULTS: Of the 47 patients studied, 23 had LVEF < 35% (low LVEF group; mean 25 +/- 7%), whereas the remaining 24 had LVEF > or = 35% (high LVEF group; mean 47 +/- 6%). In the low LVEF group, 213 segments (71%) were dysfunctional, as compared to 102 (33%) in the high LVEF group. The agreement for detection of viability between PET and SPECT in the low LVEF group was 82% (kappa 0.63), which was not different from the agreement in the high LVEF group (85%, kappa 0.66, p = 0.42 versus low LVEF group). CONCLUSIONS: The results indicate that FDG SPECT can be used for tissue viability assessment regardless of the severity of left ventricular dysfunction.

Time course of discordant BMIPP and thallium uptake after ischemia and reperfusion in a rat model.

UNLABELLED: Serial changes in fatty acid metabolism or use associated with acute ischemia and reperfusion were examined in rat hearts. METHODS: Male Wistar rats were subjected to occlusion of the left coronary artery for 20 min followed by reperfusion. After release of the occlusion, groups of animals were allowed to recover for intervals of 20 min (n = 9), 1 d (n = 9), 3 d (n = 6), 7 d (n = 6), or 30 d (n = 6). Hearts were excised 15-20 min after injection of 0.74 MBq of (125)I-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and 14.8 MBq of (201)Tl. One minute before resection, the left coronary artery was reoccluded and 185 MBq of (99m)Tc-sestamibi were injected to document the area at risk. Triple-tracer autoradiography was performed to assess tracer uptake. Uptake ratios of BMIPP and (201)Tl in the area at risk were calculated on the basis of the count density in the lesion divided by that in the normally perfused area. RESULTS: (201)Tl uptake did not change throughout the observation period (P = 0.25). In contrast, BMIPP uptake increased early in the acute phase (20 min and 1 d), decreased during the subacute phase (7 d), and subsequently recovered in the chronic phase (30 d). CONCLUSION: The present investigation clearly illustrated that BMIPP uptake is higher than (201)Tl uptake in the acute phase, that BMIPP uptake is lower than (201)Tl uptake in the subacute phase, and that BMIPP uptake and (201)Tl uptake are similar in the chronic phase. These results yield data essential to the precise interpretation of BMIPP images.

Locoreginal radioimmunotherapy with 186Re-labeled monoclonal antibody in treating small peritoneal carcinomatosis of colon cancer in mice in comparison with 131I-counterpart.

The efficacy of locoregional radioimmunotherapy (RIT) in treating peritoneal tumors of colon cancer of <2 mm in diameter was examined at maximum tolerated doses, focusing the comparison between 186Re and 131I labeled to an anti-colorectal cancer IgG1. Estimated radiation doses to tumors were considerably higher with 186Re-RIT than with 131I-RIT. The advantage of 186Re-RIT decreased with decreasing tumor size, but 186Re-RIT delivered 1.6-times higher radiation to tumors of 1 mm. Consequently, 186Re-RIT attained better survival of mice than 131I-RIT or chemotherapy with 5-fluorouracil did. Therefore, locoregional 186Re-RIT may be an option in an adjuvant setting of colon cancer with high risk of peritoneal dissemination.

Anti-angiogenic therapy and chemotherapy affect 99mTc sestamibi and 99mTc-HL91 accumulation differently in tumour xenografts.

BACKGROUND: Favourable effects of cytotoxic chemotherapy for tumours are characterized by the reduced accumulation of radiotracers such as 99mTc sestamibi (MIBI). Anti-angiogenic therapy is primarily cytostatic; consequently, its influence on tracer accumulation may differ from that of cytotoxic treatments. METHODS: Anti-angiogenic therapy employing 2-methoxyestradiol was administered in mice bearing subcutaneous xenografts of LS180 colon cancer cells. The effects of chemotherapy with 5-fluorouracil were examined as a cytotoxic counterpart. Treatments were conducted for 4 days from day 8. Distribution of 99mTc-MIBI and Tc-HL91, a hypoxic marker, was observed on days 8 and 12. Oxygen tension (PO2) in tumours was measured by a microelectrode. Cellular uptake of tracers was examined in vitro in normoxic and hypoxic conditions. RESULTS: 99mTc-MIBI accumulation decreased with increasing tumour weight when no treatment was conducted. Tumour growth was suppressed by anti-angiogenic therapy and chemotherapy. 99mTc-MIBI accumulation in tumours decreased after chemotherapy as compared to pre-therapeutic values, whereas accumulation of 99mTc-HL91 increased. In contrast, accumulation of tracers did not significantly change after anti-angiogenic therapy as compared to that observed pre-therapeutically. Tumour PO2 decreased with increasing tumour volume when no treatment was conducted. Chemotherapy reduced PO2 in tumours. PO2 in tumours treated with anti-angiogenic therapy was as high as that observed before treatment. 2-Methoxyestradiol or 5-fluorouracil did not significantly affect tracer accumulation in cells under both normoxic and hypoxic conditions in vitro. CONCLUSION: These findings indicate that scintigraphic assessment of therapeutic efficacy of anti-angiogenic therapy should be performed from a perspective distinct from that of cytotoxic treatment.

Dual-radionuclide simultaneous gastric emptying and bile transit study after gastric surgery with double-tract reconstruction.

OBJECTIVE: The physiology of gastrointestinal transfer function after proximal gastrectomy with bypass-tract reconstruction is not well understood. We applied a simultaneous dual-radionuclide method with a hepatobiliary imaging and gastric emptying study to evaluate physiologic alterations occurring after surgery. METHODS: Nineteen patients with early gastric cancer, including 9 preoperative control patients and 10 who had proximal gastrectomy and double-tract reconstruction surgery were examined by dual-radionuclide hepatobiliary and gastric emptying studies (99mTc PMT and 111In DTPA). Retention fraction in the stomach at 3 minutes (R3) and 60 minutes (R60) and gastric emptying half-time (GET) were calculated. Bile reflux and mixture of bile and food were also evaluated. RESULTS: The retention fractions of R3 and R60 were significantly lower in the double-tract reconstruction group than those in the preoperative group. GET differed significantly between the double-tract and preoperative groups (20.7 min +/- 7.1 min and 36.2 min +/- 11.0 min, p = 0.0018). The mixture of bile and food was not good in the double-tract reconstruction group (p = 0.014 vs. preoperative). Patients with a large residual stomach showed slower initial emptying (p = 0.0068) and a better mixture of bile and food (p = 0.058) compared to those with a small residual stomach. The bile reflux was not significantly increased after surgery. CONCLUSION: The dual-radionuclide gastrointestinal and hepatobiliary imaging was feasible and could demonstrate characteristic transit patterns of the foods and bile in the double-tract reconstruction procedure. A larger residual stomach, if possible, is desirable to provide better transfer and mixing of bile and foods.

Characterization of cartilaginous tumors with 201Tl scintigraphy.

UNLABELLED: Histological diagnosis and grading of cartilaginous tumors are closely correlated with patient prognosis; consequently, they are essential elements. We attempted to clarify the characteristics of 201Tl uptake in various histological types of cartilaginous tumors and to assess its clinical value. METHODS: Twenty-two cases with histologically proven cartilaginous tumors (3 enchondromas, 15 conventional chondrosarcomas (grade I = 9, II = 5, III = 1), 3 mesenchymal chondrosarcomas, and 1 de-differentiated chondrosarcoma) were examined retrospectively. Planar 201Tl images were recorded 15 min following intravenous injection of 201Tl (111 MBq). 201Tl uptake in the tumor was evaluated visually employing a five-grade scoring system: 0 = no appreciable uptake, 1 = faint uptake above the background level, 2 = moderate uptake, 3 = intense uptake but lower than heart uptake and 4 = uptake higher than heart uptake. RESULTS: 201Tl uptake scores were 0 in 3 of 3 enchondromas, 9 of 9 grade I, and 4 of 5 grade II conventional chondrosarcomas. 201Tl uptake scores were 1 among 1 of 5 grades II and a grade III conventional chondrosarcoma. Mesenchymal chondrosarcoma and de-differentiated chondrosarcoma displayed 201Tl uptake scores of 2 or 3. CONCLUSIONS: Absence of elevated 201Tl uptake in cartilaginous tumors was indicative of enchondroma or low-grade conventional chondrosarcoma. However, in instances in which 201Tl uptake is obvious, high-grade chondrosarcoma or variant types should be considered.

Accuracy of cardiac PET imaging using post-injection transmission scan.

UNLABELLED: The purpose of this study was to investigate the accuracy of cardiac PET with post-injection transmission scans. METHODS: We performed a phantom study using 18F solution as well as 13N-ammonia PET study of ten patients. The average activities of no myocardial defect phantom model were estimated, and myocardial defect sizes of 12 phantom models were measured by pre- and post-injection transmission methods at various 18F activities. In 13N-ammonia PET at rest and during adenosine triphosphate (ATP) stress studies, measured defect sizes were compared between both methods. RESULTS: The ratios of average activity estimated by both methods (post/pre value) were almost 1.00 at each 18F activity and segment. Measured defect sizes by both methods showed an excellent correlation with true defect sizes (r = 0.98, p < 0.01 for pre vs. true value: r = 0.98, p < 0.01 for post vs. true value). The mean absolute errors of measurements were minimal up to 3.5% LV, and were similar between both methods. In 13N-ammonia PET, measured defect sizes by both methods also showed a good correlation (r = 0.97, p < 0.01). CONCLUSION: The results indicate that cardiac PET imaging with post-injection transmission scan provides information on myocardial tracer activity as well as myocardial defect size as does conventional pre-injection transmission method.

Fusion of SPECT and multidetector CT images for accurate localization of pelvic sentinel lymph nodes in prostate cancer patients.

OBJECTIVE: The present study was performed to investigate the feasibility of fusion of images obtained by SPECT and multidetector CT (MDCT) for the accurate localization of sentinel lymph nodes in prostate cancer patients. METHODS: To facilitate the fusion of both SPECT and CT images, a pelvic MDCT scan was performed with 3 markers of small plastic bullets attached to the skin over the bilateral iliac crests and the ventral midline at the same height. SPECT was performed after the same locations were marked with needle caps containing (99m)Tc-pertechnetate. The images were superimposed by use of free software (MRIcro). The results of hot lymph node detection with fusion images were compared with those of surgery. RESULTS: The images could be successfully superimposed for all 11 patients examined. Surgeons accurately confirmed 27 (87.1%) of 31 regional lymph nodes on fusion images. CONCLUSION: Fusion of SPECT and MDCT images is useful for the precise localization of sentinel lymph nodes in prostate cancer patients.

Predicting the outcome of distraction osteogenesis by 3-phase bone scintigraphy.

UNLABELLED: Distraction osteogenesis is an effective method for lengthening long bones and filling bone defects that result from bone resection. Insufficiency of bone consolidation in the distraction segment is problematic. In this study, we examined whether 3-phase bone scintigraphy can predict the outcome of distraction osteogenesis. We also investigated the effects of chemotherapy and surgical treatment on distraction osteogenesis. METHODS: We performed 3-phase bone scintigraphy on 60 patients (9 high-grade malignant bone tumors as group A, 11 low-grade malignant or benign tumors as group B, 40 nontumoral conditions as group C) with distraction osteogenesis at the lengthening phase of the long bones. By setting the region of interest on the distraction segment and contralateral normal area, we calculated the perfusion index (PI), the uptake ratio of the blood-pool image (BPR), and the uptake ratio of the delayed image (DR). Patients were classified into poor and good consolidation groups from the radiographic findings of the distraction segment. RESULTS: Good to fair correlations were obtained between the PI and BPR, the PI and DR, and the BPR and DR (r = 0.65, 0.45, and 0.57, respectively). The PI and BPR indicated no significant differences among group A-C (1.7 +/- 0.6, 2.1 +/- 0.7, and 1.8 +/- 0.8 in PI, respectively; 1.8 +/- 1.1, 1.9 +/- 0.5, and 2.0 +/- 0.7, in BPR, respectively). The DR of group A (2.4 +/- 1.2) was significantly lower than that of group B (6.3 +/- 1.8; P = 0.001) and group C (5.9 +/- 2.8; P < 0.001). Eleven patients were classified in the poor consolidation group. The other 49 patients showed good consolidation. The poor consolidation group showed lower values in all indices obtained by 3-phase bone scintigraphy than the good consolidation group. The optimal cutoff levels, sensitivity, specificity, and accuracy of each index for detection of patients with poor consolidation were as follows: 1.1, 36%, 90%, and 80% in the PI, respectively; 1.2, 55%, 94%, and 87% in the BPR, respectively; and 2.2, 82%, 96%, and 93% in the DR, respectively. CONCLUSION: Three-phase bone scintigraphy is a promising method for the assessment of distraction osteogenesis. The delayed image of 3-phase bone scintigraphy, especially, is an excellent modality for predicting the outcome of distraction osteogenesis.

Prediction of myocutaneous adverse side effect due to intra-arterial chemotherapy by intra-arterial (99m)Tc-macroaggregated albumin administration in patients with bone and soft-tissue tumors.

UNLABELLED: In malignant bone and soft-tissue tumors, intra-arterial chemotherapy and limb-saving surgery have become popular. Myocutaneous inflammatory change and necrosis are the major local side effects of intra-arterial chemotherapy. (99m)Tc-macroaggregated albumin (MAA) imaging with intra-arterial tracer administration was performed to evaluate drug distribution, and the ability of (99m)Tc-MAA imaging to predict local side effects was assessed. METHODS: In 24 patients, 42 (99m)Tc-MAA images were obtained with tracer injection through an intra-arterial catheter that was inserted into the proximal portion of the tumor-feeding artery. Abnormal uptake other than by tumor was assessed visually and quantitatively. RESULTS: In visual analysis, abnormal (99m)Tc-MAA accumulation was observed in 21 of 42 images. In the first consecutive 13 of these 21 images, intra-arterial chemotherapy with cisplatin, doxorubicin, and caffeine was administered, and myocutaneous inflammation or necrosis in the area corresponding to the abnormal (99m)Tc-MAA uptake was observed in 11. In contrast, none of the 21 images without abnormal (99m)Tc-MAA uptake demonstrated any local adverse effect from intra-arterial chemotherapy. In the last consecutive 8 images with abnormal (99m)Tc-MAA uptake, intra-arterial chemotherapy was initiated with only cisplatin, and doxorubicin and caffeine administration was changed to the intravenous route. In all 8 of these images, no local adverse effects from chemotherapy were observed. Overall, the sensitivity, specificity, and accuracy of (99m)Tc-MAA imaging for the detection of myocutaneous damage were 100% (11/11), 91% (21/23), and 94% (32/34), respectively, and positive and negative predictive values were 85% (11/13) and 100% (21/21), respectively. In quantitative analysis, when the diagnostic threshold of the uptake ratio was set at 2.5, sensitivity, specificity, and accuracy for the detection of myocutaneous complications were 91% (10/11), 96% (22/23), and 94% (32/34), respectively, and positive and negative predictive values were 91% (10/11) and 96% (22/23), respectively. CONCLUSION: (99m)Tc-MAA imaging with intra-arterial infusion before intra-arterial chemotherapy for bone and soft-tissue tumors can facilitate prediction of local myocutaneous adverse effects due to chemotherapy.

Electrocardiographic gated (99m)Tc-MIBI SPECT for functional assessment of patients after coronary artery bypass surgery: comparison of wall thickening and wall motion analysis.

UNLABELLED: Abnormal septal motion after coronary artery bypass graft surgery (CABG) is a common finding. This study was undertaken to investigate the change in various global and regional ventricular function parameters measured by gated myocardial perfusion SPECT after surgery and to determine which quantitative parameter of WT and WM is more appropriate for the evaluation of regional cardiac function, especially in the septum of patients with CABG. METHODS: Before and 3 to 5 wk after CABG (all patients underwent at least 1 bypass grafting to the left anterior descending coronary artery), 35 patients (28 men, 7 women) underwent gated SPECT using (99m)Tc-methoxyisobutylisonitrile. Quantitative global and regional ventricular functional analysis was performed using quantitative gated SPECT software. RESULTS: Global ejection fraction did not change (59.3% +/- 16.0% to 60.5% +/- 14.5%, P = 0.24). However, end-diastolic and end-systolic volumes lessened significantly after CABG (81.4 +/- 37.3 mL to 68.9 +/- 28.9 mL, P < 0.0001, and 38.1 +/- 33.1 mL to 30.4 +/- 23.0 mL, P < 0.005, respectively). As global function parameters, the changes in both total WM (r = 0.88) and WT (r = 0.86) correlated well with the change in ejection fraction after surgery. Segmental analysis showed a significant postoperative increase in relative tracer uptake in the anterior, anteroseptal, inferoseptal, and inferior walls and in the apex. Segmental wall motion (WM) deteriorated in the anteroseptal, inferoseptal, and mid anterior walls. On the other hand, anterolateral, inferolateral, and inferior WM increased. As a whole, these WM changes showed a reduction in septal motion associated with a concomitant increase in lateral motion after surgery. Segmental wall thickening, however, did not decrease in septal areas and did not increase in the lateral wall and correlated with percentage tracer uptake (r = 0.69) better than WM did (r = 0.30) after CABG. CONCLUSION: In patients with CABG, postoperative WM analysis by gated SPECT underestimated septal motion and overestimated lateral motion because of exaggerated systolic anteromedial cardiac translation. Therefore, wall thickening analysis would be recommended for the evaluation of postoperative cardiac function.

Detection of cardiomyocyte death in a rat model of ischemia and reperfusion using 99mTc-labeled annexin V.

UNLABELLED: There is increasing evidence that cell death after myocardial ischemia and reperfusion may begin as apoptosis rather than necrosis. To determine the time course, location, and extent of this process, we studied groups of rats after a 20-min interval of coronary occlusion and reperfusion. METHODS: After thoracotomy, the left coronary artery was occluded for 20 min. After release and before study, groups of animals were allowed to recover for various intervals: 0.5 h (n = 6), 1.5 h (n = 7), 6 h (n = 7), 1 d (n = 8), 3 d (n = 8), or 2 wk (n = 5). At the time of study, the rats were injected with 99mTc-annexin V (80-150 MBq). One hour later, to verify the area at risk, 201Tl (0.74 MBq) was injected intravenously just after the left coronary artery reocclusion and the rats were sacrificed 1 min later. Dual-tracer autoradiography was performed to assess 99mTc-annexin V uptake and the area at risk. RESULTS: Extensive 99mTc-annexin V uptake was observed in the mid myocardium after 0.5-1.5 h of reperfusion. The area of annexin uptake had expanded in the subendocardial and subepicardial layers at 6 h after reperfusion and then gradually lessened over 3 d. At 0.5 and 1.5 h of reperfusion, 99mTc-annexin V uptake ratios were 7.36 +/- 2.95 and 6.34 +/- 2.24 (mean +/- SD), respectively. The uptake ratios gradually decreased at 6 h, 1 d, 3 d, and 2 wk after reperfusion (4.65 +/- 1.93, 3.27 +/- 0.92 [P < 0.01 vs. 0.5 h], 1.84 +/- 0.55 [P < 0.001 vs. 0.5 h, P < 0.005 vs. 1.5 h], and 1.65 +/- 0.31 [P < 0.001 vs. 0.5 h, P < 0.005 vs. 1.5 h], respectively). CONCLUSION: These data indicate that annexin binding commences soon after ischemia and reperfusion in the mid myocardium within the area at risk and expands to include the subendocardial and subepicardial layers at 6 h after reperfusion, followed by gradual reduction of activity over 3 d.

Cooperative effect of radioimmunotherapy and antiangiogenic therapy with thalidomide in human cancer xenografts.

UNLABELLED: Antiangiogenic therapy may prolong the dormancy of cancer lesions. Moreover, radioimmunotherapy (RIT) may eradicate this population of cells. This study dealt with determining the benefits associated with the combined usefulness of these 2 therapies with respect to inhibition of tumor growth. METHODS: Antiangiogenic therapy using oral thalidomide (daily dose, 200 mg/kg) and RIT involving a single intravenous injection (4.63 MBq (131)I-A7, an IgG1 murine monoclonal antibody) were conducted in mice bearing LS180 human colon cancer xenografts. RIT with an irrelevant IgG1, HPMS-1, was also performed as a control. Antiangiogenesis of thalidomide was investigated by immunohistochemical analysis of tumor sections. RESULTS: Antiangiogenic therapy and RIT with (131)I-A7 significantly suppressed the growth of xenografts. This combination produced more efficient tumor growth inhibition than did the monotherapy (P < 0.005). RIT using (131)I-HPMS-1 was far less effective than (131)I-A7, even when combined with thalidomide administration. Immunohistochemistry revealed a decrease in the microvessel number within tumors treated with thalidomide (P < 0.0001). Combined therapy further reduced the microvessel number (P < 0.01 vs. thalidomide monotherapy). CONCLUSION: The combination of RIT and thalidomide antiangiogenic therapy produces a better response of tumors than does monotherapy. Acting in concert, antiangiogenic therapy may prolong the dormancy of cancer lesions and RIT may eradicate this population of cells.

Feasibility of 186Re-radioimmunotherapy for treatment in an adjuvant setting of colon cancer.

PURPOSE: (186)Re displays abundant intermediate energy beta emission, and possesses an appropriate physical half-life of 3.7 days. We compared the efficacy of radioimmunotherapy (RIT) with an anti-colorectal cancer monoclonal IgG1, (186)Re-A7, with that of RIT employing (131)I in a mouse liver metastasis model. METHODS: Liver metastases were established by intrasplenic injection of LS180 human colon cancer cells. Based on the results of toxicity assessment with escalated administration doses, 21 MBq (186)Re-A7 and 7 MBq (131)I-A7 were chosen as maximum tolerated doses. In the first experiment, mice underwent RIT at 2 weeks when metastases attain a diameter of several millimeters, and were killed 2 weeks later to assess metastatic burden in the liver. In the second experiment, RIT was conducted at 1 week when metastases of several hundred micrometers in diameter were observed, and survival of mice was examined. RESULTS: (186)Re-A7 RIT inhibited the growth of liver metastases better than (131)I-A7 RIT ( P<0.02). Furthermore, (186)Re-A7 RIT induced better improvement in survival of mice than (131)I-A7 RIT ( P<0.002). (186)Re-A7 RIT caused slightly more severe myelotoxicity in mice, but they eventually recovered. Radiation dose estimation demonstrated a significant advantage of (186)Re-A7 RIT over (131)I-A7 RIT. CONCLUSION: These results support the use of RIT with (186)Re-MAb in an adjuvant setting in cases involving minimal disease.

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.