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1.
Auris Nasus Larynx ; 47(6): 1054-1057, 2020 Dec.
Article in English | MEDLINE | ID: mdl-31899060

ABSTRACT

Silicosis is caused by inhalation of silica dust and is the most common type of pneumoconiosis. The characteristics of silicosis are inflammation of lung tissue and calcified lymphadenopathy of pulmonary hilum, mediastinum and paratrachea. We present a papillary thyroid carcinoma (PTC) case with paratracheal and superior mediastinal calcified lymphadenopathy caused by silicosis. The patient did not exhibit any respiratory symptoms or abnormal chest x-ray findings due to early phase silicosis. The lymph nodes were thought to be metastasis of PTC before surgery. Patient underwent total thyroidectomy with neck and superior mediastinum dissection. Post-surgery pathological examination exhibited coexistence of silica nodules and micrometastasis of PTC in paratracheal lymph nodes, but only silica nodules were observed in superior mediastinum lymph nodes. Patient's occupation was office worker but had worked as a stonemason for several decades prior. This is a first observed case of superior mediastinal lymphadenopathy by silicosis mimicking metastasis of PTC. Benign calcified lymphadenopathy may mimic metastasis of PTC in the evaluation of neck or mediastinal lesions.


Subject(s)
Lymphadenopathy/diagnosis , Lymphatic Metastasis/diagnosis , Silicosis/complications , Thyroid Cancer, Papillary/secondary , Thyroid Neoplasms/pathology , Diagnosis, Differential , Humans , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphadenopathy/etiology , Male , Mediastinum , Middle Aged , Silicosis/diagnosis , Thyroid Cancer, Papillary/diagnosis , Tomography, X-Ray Computed
4.
Ann Nucl Med ; 21(6): 367-9, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17705018

ABSTRACT

Airway complications rarely occur in 131I radioiodine therapy for Graves' disease. This study presents two cases in which 131I therapy caused this acute complication. The patients complained of the symptom 6 h and 33 h after administration of 131I. A histamine H1 receptor antagonist and hydrocortisone rapidly resolved symptoms in both cases. These two cases remind physicians that 131I therapy for Graves' disease may cause potentially life-threatening complications.


Subject(s)
Airway Obstruction/diagnosis , Airway Obstruction/etiology , Graves Disease/radiotherapy , Iodine Radioisotopes/adverse effects , Iodine Radioisotopes/therapeutic use , Radiation Injuries/diagnosis , Radiation Injuries/etiology , Adult , Airway Obstruction/prevention & control , Female , Graves Disease/complications , Humans , Middle Aged , Radiation Injuries/prevention & control
5.
Nucl Med Commun ; 28(2): 129-33, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17198354

ABSTRACT

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.


Subject(s)
Colonic Neoplasms/therapy , Injections, Intraperitoneal/methods , Peritoneal Neoplasms/therapy , Radioimmunotherapy/methods , Animals , Antibodies, Monoclonal/chemistry , Cell Line, Tumor , Female , Humans , Male , Mice , Mice, Inbred BALB C , Neoplasm Metastasis , Time Factors
6.
Ann Nucl Med ; 20(7): 499-502, 2006 Aug.
Article in English | MEDLINE | ID: mdl-17037283

ABSTRACT

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.


Subject(s)
Iodine Radioisotopes/adverse effects , Iodine Radioisotopes/therapeutic use , Lung Injury , Lung/pathology , Radiation Injuries , Radiotherapy/adverse effects , Thyroid Neoplasms/radiotherapy , Aged , Carcinoma, Papillary/radiotherapy , Edema/pathology , Female , Humans , Lung Neoplasms/secondary , Middle Aged , Neck/pathology , Neoplasm Metastasis , Time Factors
7.
Ann Nucl Med ; 20(1): 29-34, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16485571

ABSTRACT

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.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , Oligodeoxyribonucleotides, Antisense/administration & dosage , Technetium Tc 99m Sestamibi/pharmacokinetics , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Cell Line, Tumor , Genetic Therapy/methods , Humans , Metabolic Clearance Rate , Oligodeoxyribonucleotides, Antisense/genetics , Prognosis , RNA, Messenger/genetics , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Treatment Outcome
8.
Cancer Biother Radiopharm ; 21(1): 34-40, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16480329

ABSTRACT

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.


Subject(s)
Indium Radioisotopes/pharmacokinetics , Leukemia P388/metabolism , Oligodeoxyribonucleotides/pharmacokinetics , Animals , Biological Transport , Cell Line, Tumor , Doxorubicin/toxicity , Drug Resistance, Neoplasm , Humans , Indium Radioisotopes/therapeutic use , Kinetics , Leukemia P388/radiotherapy , Mice , Oligodeoxyribonucleotides/blood , Oligodeoxyribonucleotides/therapeutic use
9.
Nucl Med Commun ; 26(12): 1067-73, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16264352

ABSTRACT

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.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Neovascularization, Pathologic , Organotechnetium Compounds/pharmacokinetics , Oximes/pharmacokinetics , Technetium Tc 99m Sestamibi/pharmacokinetics , 2-Methoxyestradiol , Animals , Cell Line, Tumor , Estradiol/analogs & derivatives , Estradiol/pharmacology , Fluorouracil/pharmacology , Humans , Hypoxia , Kinetics , Mice , Neoplasm Transplantation , Oxygen/metabolism , Radiopharmaceuticals/pharmacokinetics , Time Factors
10.
Cancer Lett ; 219(1): 41-8, 2005 Feb 28.
Article in English | MEDLINE | ID: mdl-15694663

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Colonic Neoplasms/radiotherapy , Iodine Radioisotopes/administration & dosage , Peritoneal Neoplasms/radiotherapy , Radioimmunotherapy , Rhenium/administration & dosage , Animals , Disease Models, Animal , Injections, Intraperitoneal , Iodine Radioisotopes/pharmacokinetics , Maximum Tolerated Dose , Mice , Peritoneal Neoplasms/secondary , Radioimmunotherapy/methods , Radioisotopes/pharmacokinetics , Rhenium/pharmacokinetics , Tissue Distribution
11.
Ann Nucl Med ; 18(7): 631-2, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15586639

ABSTRACT

We experienced a case with Graves' disease in which radioiodine treatment failed probably because of intentional spitting out of capsules of radioactive iodide. Chemical analysis of the substances collected from the trash in the treatment room demonstrated that its profile was the same as that of the capsules for radioiodine administration. Measurement of the iodine concentrations in a blood sample obtained at 24 h after the administration of radioiodine indicated that the patient showed iodine excess. These findings suggest that this may be a case of Munchausen syndrome.


Subject(s)
Graves Disease/radiotherapy , Iodine Radioisotopes/therapeutic use , Munchausen Syndrome/diagnosis , Treatment Failure , Treatment Refusal , Adult , Female , Graves Disease/blood , Graves Disease/complications , Graves Disease/diagnosis , Humans , Iodine Radioisotopes/blood , Munchausen Syndrome/complications , Radiopharmaceuticals/blood , Radiopharmaceuticals/therapeutic use
12.
Ann Nucl Med ; 18(4): 345-9, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15359929

ABSTRACT

OBJECTIVE: This study was performed to clarify factors that might influence short-term side effects occurring within 96 hours after administration of 131I for patients with thyroid carcinoma. METHODS: In 71 patients with differentiated thyroid carcinoma, short-term side effects including gastrointestinal complaints, salivary gland swelling with pain, change in taste and headache were retrospectively analyzed. All patients were given domperidone for prevention of gastrointestinal complaints and advised to consume sour foods to promote discharge of radioiodine from the salivary glands. Selected factors possibly affecting the incidence of side effects were dose per body weight, TSH, effective half-life of 131I, sex, age, 131I accumulation into the stomach and salivary glands, and edema prior to radioiodine administration. The factors were evaluated by multivariate analyses. RESULTS: Incidence of gastrointestinal complaints, salivary gland swelling with pain, change in taste and headache was 65.2%, 50.0%, 9.8% and 4.4%, respectively. In gastrointestinal complaints, the incidence of appetite loss, nausea and vomiting was 60.9%, 40.2% and 7.6%, respectively. The gastrointestinal complaints increased significantly in the patients dosed above 55.5 MBq/kg and with TSH elevation. For salivary gland swelling with pain, female patients displayed a significantly higher incidence than males. No statistically significant factors were detected for change in taste or headache. CONCLUSIONS: Significant factors influencing short-term side effects were dose per body weight and TSH values for gastrointestinal complaints, and female sex for salivary gland swelling with pain. Our preliminary experience suggests that the most frequent gastrointestinal complaints can be prevented with ramosetron.


Subject(s)
Gastrointestinal Diseases/epidemiology , Iodine Radioisotopes/therapeutic use , Pain/epidemiology , Radiation Injuries/epidemiology , Risk Assessment/methods , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/radiotherapy , Adolescent , Adult , Aged , Causality , Comorbidity , Dose-Response Relationship, Radiation , Edema/epidemiology , Female , Humans , Japan/epidemiology , Middle Aged , Radiopharmaceuticals , Retrospective Studies , Risk Factors , Sex Distribution , Time Factors , Treatment Outcome
13.
Eur J Nucl Med Mol Imaging ; 31(11): 1523-9, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15449049

ABSTRACT

PURPOSE: The feasibility of intracellular mdr1 mRNA expression detection with radiolabeled antisense oligonucleotide (ODN) was investigated in the murine leukemia cell line, P388/S, and its subclonal, adriamycin-resistant cell line, P388/R. METHODS: The expression level of mdr1 mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Existence of the multidrug resistance (MDR) phenomenon was assessed via cellular uptake of 99mTc-sestamibi (MIBI), a known substrate for P-glycoprotein. A 15-mer phosphorothioate antisense ODN complementary to the sequences located at -1 to 14 of mdr1 mRNA and its corresponding sense ODN were conjugated with the cyclic anhydride of diethylene triamine penta-acetic acid (cDTPA) via an amino group linked to the terminal phosphate at the 5' end at pH 8-9. The DTPA-ODN complexes at concentrations of 0.1-17.4 microM were reacted with 111InCl3 at pH 5 for 1 h. The hybridization affinity of labeled ODN was evaluated with size-exclusion high-performance liquid chromatography following incubation with the complementary sequence. Cellular uptake of labeled ODN was examined in vitro. Furthermore, enhancing effects of synthetic lipid carriers (Transfast) on transmembrane delivery of ODN were assessed. RESULTS: P388/R cells displayed intense mdr1 mRNA expression in comparison with P388/S cells. 99mTc-MIBI uptake in P388/S cells was higher than that in P388/R cells. Specific radioactivity up to 1,634 MBq/nmol was achieved via elevation of added radioactivity relative to ODN molar amount. The hybridization affinity of antisense 111In-ODN was preserved at approximately 85% irrespective of specific activity. Cellular uptake of antisense 111In-ODN did not differ from that of sense 111In-ODN in either P388/S cells or P388/R cells. However, lipid carrier incorporation significantly increased transmembrane delivery of 111In-ODN; moreover, specific uptake of antisense 111In-ODN was demonstrated in P388/R cells. CONCLUSION: Radiolabeling of ODN at high specific radioactivity and specific uptake of antisense 111In-ODN in drug-resistant cells may facilitate future gene imaging of mdr1 mRNA.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Indium Radioisotopes/pharmacokinetics , Leukemia/diagnostic imaging , Leukemia/metabolism , Oligonucleotides/pharmacokinetics , RNA/metabolism , Animals , Cell Line, Tumor , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Feasibility Studies , Leukemia/genetics , Metabolic Clearance Rate , Mice , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics
14.
Ann Nucl Med ; 18(2): 151-5, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15195763

ABSTRACT

OBJECTIVE: Patients with Graves' disease were studied one year after radioiodine-131 therapy to assess the relationship between the effectiveness of the therapy and the radioiodine doses used. METHODS: Patients were classified into three groups according to thyroid function as hyperthyroidism, euthyroidism and hypothyroidism at one year after I-131 therapy. In these groups we compared the mean values of dose, dose per thyroid weight calculated with I-123 uptake before the therapy (pre D/W), dose per thyroid weight calculated with therapeutic I-131 uptake (post D/W), and absorbed dose. RESULTS: No significant differences were found between the three groups in terms of dose or pre D/W. The mean values of post D/W and absorbed dose in the non-hyperthyroid (euthyroid and hypothyroid) group were significantly greater than those in the hyperthyroid group. Post D/W of 6.3 MBq/g was a threshold separating the non-hyperthyroid group from the hyperthyroid group. There was no correlation between pre D/W and post D/W; however, the mean post D/W was significantly greater than the mean pre D/W. All patients with pre D/W above 6.3 MBq/g showed non-hyperthyroidism at one year after the radioiodine treatment. CONCLUSIONS: No indicators before the radioiodine therapy had significant relationships with the effectiveness of the therapy at one year after the treatment. However, the single therapy planned for setting the pre D/W above 6.3 MBq/g will certainly make the patients non-hyperthyroid. As this proposal of dose planning is based on a small number of patients, further study is needed.


Subject(s)
Graves Disease/diagnosis , Graves Disease/radiotherapy , Iodine Radioisotopes/administration & dosage , Radiometry/methods , Radiopharmaceuticals/administration & dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Computer-Assisted/methods , Adult , Aged , Dose Fractionation, Radiation , Female , Humans , Male , Radiotherapy Dosage , Treatment Outcome
15.
Nucl Med Commun ; 25(6): 585-9, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15167518

ABSTRACT

BACKGROUND: Previous reports have demonstrated the feasibility of scintigraphic assessment of the multi-drug resistance (MDR) of tumours caused by ATP binding cassette (ABC) transporters by using Tc cationic tracers such as Tc tetrofosmin (TF). Furthermore, the potential of these tracers for evaluating the effects of reversal agents for MDR has been documented. However, most reversal agents simultaneously affect cationic ion transporters related to tracer accumulation in tumours. METHODS: The uptake of Tc-TF was examined in the MCF7/WT cell line, a wild-type breast cancer cell line that does not exhibit MDR, and its subclonal etoposide resistant cell line MCF7/VP, which expresses high levels of MRP1, one of the multi-drug resistance associated proteins (MRPs), in the presence of increasing concentrations of verapamil, a classical MDR modulator. In the absence of verapamil, MCF7/VP cells showed significantly lower Tc-TF uptake than did MCF7/WT cells, indicating that Tc-TF is a substrate for MRP1. The presence of verapamil enhanced the uptake of Tc-TF in MCF7/VP cells. On the other hand, verapamil also increased tracer uptake in MCF7/WT cells, which was readily appreciated when the uptake values were corrected by viable cell numbers: an approximately 100% increase of Tc-TF uptake was observed in comparison with that in the absence of verapamil in viable MCF7/WT cells whereas a 100-200% increase occurred in viable MCF7/VP cells. In addition, verapamil prolonged the retention of radioactivity in both MCF7/WT cells and MCF7/VP cells. CONCLUSION: These results suggest that cellular functions other than MRP1 function, probably cationic ion transporters, are simultaneously and significantly involved in the verapamil induced changes of cellular uptake of Tc-TF. Tc-TF scintigraphy may overestimate the reversal effects of modulators on chemoresistance caused by MRP1 when the modulators simultaneously affect ion transporters.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Drug Resistance, Multiple/drug effects , Organophosphorus Compounds/pharmacokinetics , Organotechnetium Compounds/pharmacokinetics , Verapamil/administration & dosage , Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Treatment Outcome
16.
Eur J Nucl Med Mol Imaging ; 31(7): 981-5, 2004 Jul.
Article in English | MEDLINE | ID: mdl-14991242

ABSTRACT

We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of (131)I-A7, an IgG1 anti-colorectal monoclonal antibody, or (131)I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation ( n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice ( n=8) ( P<0.05). (131)I-A7 RIT displayed a marked therapeutic effect ( n=8) ( P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of (131)I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy ( n=10) ( P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and (131)I-HPMS-1 RIT failed to provide an appreciable benefit ( n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Biomarkers, Tumor/metabolism , Iodine Radioisotopes/administration & dosage , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms, Experimental/therapy , Radioimmunotherapy/methods , Vascular Endothelial Growth Factor A/metabolism , Animals , Cell Line, Tumor , Colonic Neoplasms/metabolism , Colonic Neoplasms/therapy , Combined Modality Therapy/methods , Dose-Response Relationship, Drug , Female , Liver Neoplasms, Experimental/secondary , Mice , Mice, Inbred BALB C , Mice, Nude , Radiopharmaceuticals/administration & dosage , Survival Analysis , Treatment Outcome
17.
Ann Nucl Med ; 17(7): 619-24, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14651366

ABSTRACT

OBJECTIVES: We observed whether clearer tumor delineation and greater tumor to non-tumor (T/N) count ratios could be obtained using an iterative ordered-subsets expectation maximization (OSEM) algorithm than conventional filtered-back projection algorithm (FBP) in the image reconstruction of thallium-201 (201Tl) lung scintigraphy. METHODS: In 29 patients with lung cancer and phantom studies, tomograms were reconstructed using FBP and OSEM algorithms, with and without a prefilter (Butterworth filter: BW), whose cut-off frequencies were 0.10 cycles/pixel for FBP and 0.10 and 0.17 cycles/pixel for OSEM. Visual interpretation and tumor to non-tumor (T/N) count ratios were obtained and compared. RESULTS: Without a prefilter, T/N ratios from OSEM and FBP were 1.89 +/- 0.31 (early) and 2.00 +/- 0.54 (late) for OSEM, 1.90 +/- 0.33 (early) and 2.05 +/- 0.59 (late) for FBP, respectively. The OSEM reconstruction without prefiltering showed clearer tumor contours than FBP without a prefilter. Incorporation of BW showed visually low-noised images but decreased T/N ratios in both reconstructions with BW (0.10 cycles/pixel). No greater T/N ratios were obtained by OSEM than FBP, with or without prefiltering. With BW with a cut-off frequency of 0.17 cycles/pixel, the same T/N ratios as those without BW were obtained. The tumor model sized 0.9 cm in the phantom study was invisible in both OSEM and FBP reconstructions without a prefilter, but visible with a prefilter. The influence of prefiltering on T/N ratios was also observed in phantom studies. CONCLUSIONS: Visually improved tumor delineation could be obtained in OSEM reconstruction without a prefilter as compared to FBP reconstruction without a prefilter for tumors greater than 2 cm. Prefiltering should be incorporated into OSEM reconstruction in diagnosing small tumors. However, the influence of prefilter (BW) setting on semi-quantitative interpretation needs further discussion.


Subject(s)
Algorithms , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Solitary Pulmonary Nodule/diagnostic imaging , Thallium , Tomography, Emission-Computed, Single-Photon/methods , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging/methods , Pilot Projects , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Solitary Pulmonary Nodule/pathology
18.
J Cancer Res Clin Oncol ; 129(7): 392-6, 2003 Jul.
Article in English | MEDLINE | ID: mdl-14605881

ABSTRACT

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.


Subject(s)
Colonic Neoplasms/pathology , Immunoconjugates/therapeutic use , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Radioimmunotherapy , Radioisotopes/therapeutic use , Rhenium/therapeutic use , Animals , Disease Models, Animal , Female , Humans , Iodine Radioisotopes/therapeutic use , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Radioisotopes/administration & dosage , Radiotherapy Dosage , Rhenium/administration & dosage
19.
Eur J Nucl Med Mol Imaging ; 30(11): 1529-31, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14579093

ABSTRACT

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of (99m)Tc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, (99m)Tc-tetrofosmin (TF), was also examined. Cellular uptake of (99m)Tc-MIBI and (99m)Tc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N(2) and 5% CO(2) reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Multidrug Resistance-Associated Proteins/metabolism , Organophosphorus Compounds/pharmacokinetics , Organotechnetium Compounds/pharmacokinetics , Oxygen/metabolism , Technetium Tc 99m Sestamibi/pharmacokinetics , Cell Hypoxia , Cell Line, Tumor , Humans , Metabolic Clearance Rate , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics
20.
Cancer Sci ; 94(7): 650-4, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12841877

ABSTRACT

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.


Subject(s)
Colonic Neoplasms/radiotherapy , Peritoneal Neoplasms/radiotherapy , Peritoneal Neoplasms/secondary , Radioimmunotherapy/methods , Animals , Colonic Neoplasms/pathology , Mice , Platelet Count , Survival Analysis , Time Factors , Tumor Cells, Cultured , Weight Loss/radiation effects
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