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Biomedical subjects

N Shuke

Publications and source records attributed to N Shuke.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enhanced efficacy of radioimmunotherapy combined with systemic chemotherapy and local hyperthermia in xenograft model.

We previously found that the efficacy of radioimmunotherapy (RIT) with (131)I-A7, an IgG(1) against M(r) 45000 glycoprotein on colon cancer, was enhanced by local hyperthermia (HT) or chemotherapy with 5-fluorouracil (5-FU). In this study, we aimed to further enhance its efficacy by combining these three modalities. Human colon cancer xenografts (146 x 12 mm(3)) in Balb / c nu / nu female mice were treated with 9.25 MBq (131)I-A7 i.v. combined with HT (43 degrees C for 1 h) and 5-FU (30 mg / kg / day i.p. for 5 days). Tumor growth delay, (Tq(treated) - Tq(control) )/ Tq(control) where Tq is tumor quadrupling time, in mice treated with RIT + HT + 5-FU was improved to 12.7 from 5.90, 7.55 and 10.1 with RIT alone, RIT + 5-FU and RIT + HT, respectively. Complete response was observed in 4 out of 8 tumors with RIT + HT + 5-FU and 3 out of 10 with RIT + HT. No tumor showed complete response with RIT + 5-FU or RIT alone. 5-FU slightly increased myelotoxicity of RIT, but HT did not affect it. Body weight loss was not enhanced by the combination. These results indicate that the combination of three modalities is a feasible approach to enhance the antitumor efficacy of RIT without serious increase of toxicity.

Animals↗
PubMed2000

Pharmacologic intervention with angiotensin II and kininase inhibitor enhanced efficacy of radioimmunotherapy in human colon cancer xenografts.

UNLABELLED: Induced hypertension and kininase inhibition can enhance tumor targeting of radiolabeled monoclonal antibody (MAb) by altering tumor circulation. This study investigated the effect of this manipulation on the antitumor efficacy of radioimmunotherapy (RIT). METHODS: Mice bearing human colon cancer xenografts were administered 2.0 microg/kg/min of angiotensin II (AT-II) for 1 h and 30 microg of a kininase inhibitor, enalapril maleate, before the administration of 3.7 MBq (131)I-A7, an IgG1 against 45-kDa glycoprotein on colorectal cancer, and tumor growth was observed thereafter. The mechanism of the manipulation effect was investigated by estimation of the tissue absorbed dose and radioluminography of tumors. RESULTS: The pharmacologic manipulation with AT-II and enalapril improved the tumor quadrupling time (Tq) of 3.7 MBq RIT from 24.3 +/- 2.75 d to 33.1 +/- 2.83 d (P < 0.05). Addition of this manipulation made 3.7 MBq RIT as effective as 9.25 MBq RIT alone (Tq, 37.2 +/- 2.97 d). Dose estimation showed that the manipulation increased the tumor absorbed dose 1.55-fold without affecting the doses to normal tissues. Uniform intratumoral distribution in the manipulated tumors was shown by radioluminography. CONCLUSION: Larger and more uniform tumor radiation produced by this pharmacologic manipulation can benefit RIT with (131)I-MAb.

Angiotensin II↗
PubMed1999

Combination radioimmunotherapy with local hyperthermia: increased delivery of radioimmunoconjugate by vascular effect and its retention by increased antigen expression in colon cancer xenografts.

Hyperthermia (HT) may increase tumor targeting of a radiolabeled antibody by its effects on tumor vasculature and antigen expression. Expression of a 45-kDa glycoprotein antigen on LS180 colon cancer cells was 2.7-fold enhanced 2 days after heating at 43 degrees C for 1 h. Preferential tumor accumulation of 125I-A7 recognizing this antigen was doubled and the antitumor effect of 131I-A7 was significantly improved by HT. Hyperthermia also increased tumor uptake of an irrelevant antibody but its radioactivity was rapidly cleared. These results indicate that HT increased the initial delivery of an antibody to a tumor by its vascular effect, and radioactivity was retained in tumors by increased specific binding, resulting in a better radioimmunotherapy outcome.

Animals↗
PubMed1999

Sub-super bone scan caused by bone marrow involvement of prostate cancer.

A 67-year-old man presented with malaise and marked anemia. A diagnostic workup revealed severe pancytopenia on a complete blood count and diffuse sclerotic change in the axial skeleton on a plain abdominal radiograph. Bone metastases being suspected from these findings, bone scintigraphy was performed. The bone scan demonstrated uniformly increased skeletal activity with faint soft-tissue activity. The findings of the bone scan, however, appeared atypical of the super scan caused by diffuse bone metastases, without any decrease in radioactivities of the appendicular skeleton and kidneys. Bone marrow scintigraphy with In-111 chloride demonstrated central marrow failure and peripheral expansion, which indicated the possibility of myelophthisis. The patient underwent bone marrow biopsy, which revealed replacement of the bone marrow by metastatic adenocarcinoma. Further examinations detected the primary lesion in the prostate. In this case, the findings of the bone scan were insufficient for the super scan, and might be categorized as a sub-super scan. It would be important to recognize this incomplete form of super scan as a rare scintigraphic pattern of diffuse bone marrow metastases.

Adenocarcinoma↗
PubMed1999

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

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

Animals↗
PubMed1999

Experimental investigation of I-123 iodoamphetamine in the detection of lung cancer.

Experimentally we investigated the detection of lung cancer with N-isopropyl-p-I-123-iodoamphetamine (I-123 IMP). Various tumors including Lewis lung cancer were used as tumor models. Serial images were obtained. Biodistribution of Lewis lung cancer was performed. In Lewis lung cancer good visualization as in B-16 melanoma and high tumor accumulation were found with IMP. In conclusion, due to its greater accumulation almost equivalent to that in melanotic melanoma, I-123 IMP may have a role in the detection of lung cancer.

Animals↗
PubMed1999

Differential uptake of TI-201 by small-cell lung cancer in a patient with pneumoconiosis-related pulmonary nodules.

A 68-year-old man with pneumoconiosis was thought to have small-cell lung cancer based on the results of a biopsy of a bone tumor. Three pulmonary nodules were observed on a chest radiograph. Compared with a chest radiograph taken 4 months earlier, one of the nodules had grown. It was difficult to differentiate this nodule from pneumoconiosis-related benign pulmonary nodules from the appearance on the chest radiograph and CT. Ga-67 scintigraphy and TI-201 lung SPECT were performed to characterize these nodules. TI-201 SPECT showed differential high uptake in the enlarged nodule, whereas Ga-67 scintigraphy showed equally intense uptake in all these nodules. Transbronchial biopsy of the nodule that showed high TI-201 uptake revealed cancer cell nests against a background of interstitial fibrosis. The pathologic diagnosis was small-cell lung cancer that had developed in lung scar tissue. This case suggests the utility of TI-201 in scintigraphic assessments of pneumoconiosis-related pulmonary nodules when lung cancer is suspected.

Aged↗
PubMed1999

Early response of tumour to radiotherapy should be assessed by both uptake and retention of single photon tracers: in vitro analysis with 201Tl-chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin in human bladder cancer cells and human leukocytes.

The uptake and retention of single photon tracers in irradiated tumour cells was observed in an attempt at the early evaluation of the effect of radiation. T24 human bladder cancer cells were exposed to a single dose of 10 Gy or 20 Gy or a fractionated dose of 10 Gy (2 Gy for 5 days). The uptake of 201Tl chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin was observed by incubating in vitro for 60 min. The retention of the tracers was observed at 60 min after changing the incubation medium for a tracer-free medium. Uptake per culture well of all tracers in the cells exposed to 20 Gy declined as viable cell number decreased, but uptake per cell increased progressively. Uptake per cell of all tracers in the cells exposed to either a single dose or a fractionated dose of 10 Gy also increased, while a delay in growth was observed. The retention of these tracers decreased during this period and recovered thereafter. A binding assay with purified human leukocytes indicated that assessment with 99Tcm-sestamibi and 99Tcm-tetrofosmin is influenced by inflammatory cells. In conclusion, the effect of radiation may be underestimated if assessed by tracer uptake alone because of the increase in tracer uptake in viable irradiated cells. Observation of the retention of tracers may provide additional information.

Humans↗
PubMed1999

Multiple myeloma evaluated with 201Tl scintigraphy compared with bone scintigraphy.

UNLABELLED: The purpose of this study was to investigate the clinical usefulness of 201Tl chloride scintigraphy in the diagnostic evaluation of 20 patients with multiple myeloma (19/20 patients) or extramedullary plasmacytoma (1/20 patients) in comparison with bone scintigraphy. METHODS: Both 201Tl and bone scintigraphy were performed to obtain planar images on the same instrument. RESULTS: 201Tl scintigraphy showed increased uptake in 15 of 20 patients (75%) and was negative in 5 of 20 patients (25%). In addition, 201Tl scintigraphy of multiple myeloma was more useful in detecting the lesions in 11 of 17 patients and less useful in 6 of 17 patients than bone scintigraphy. CONCLUSION: The combination of 201Tl and bone scintigraphy, compared with bone scintigraphy alone, shows promise in more accurately diagnosing multiple myeloma.

Bone Neoplasms↗
PubMed1999

Preoperative assessment of residual hepatic functional reserve using 99mTc-DTPA-galactosyl-human serum albumin dynamic SPECT.

UNLABELLED: Preoperative assessment of residual hepatic functional reserve offers important strategic information for hepatic resection. To predict the postoperative residual liver function, we assessed the value of hepatic 99mTc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) clearance estimated by dynamic SPECT analysis. METHODS: We investigated 114 consecutive patients with liver disease, including 55 hepatectomy cases. One minute after injection of 185 MBq 99mTc-GSA, 15 serial dynamic SPECT images were obtained every minute. The initial five sets of SPECT images were analyzed by Patlak plot to estimate the sequential initial hepatic 99mTc-GSA clearance (mL/min) as an index of hepatic function. The sum of hepatic 99mTc-GSA clearance of the segments immune from resection was categorized as predicted residual 99mTC-GSA clearance. In the hepatectomy cases, scintigraphy was performed before and 37 +/- 10 d after the operation. RESULTS: Good correlation was observed between the total hepatic 99mTc-GSA clearance and conventional hepatic function tests: plasma retention rate of iodocyanine green (ICG) at 15 min (ICG R15), r = -0.600, P < 0.0001, n = 94; plasma disappearance rate of ICG (K ICG), r = 0.670, P < 0.0001, n = 83; cholinesterase, r = 0.539, P < 0.0001, n = 121; serum albumin, r = 0.421, P = 0.0001, n = 123; and hepaplastin test, r = 0.456, P < 0.0001, n = 120. There was good correlation between the predicted residual 99mTc-GSA clearance and the postoperative total hepatic 99mTc-GSA clearance in patients who underwent segmentectomy or lobectomy (r = 0.84, P < 0.0001, n = 28) and between the pre- and postoperative total hepatic 99mTc-GSA clearance in patients who underwent subsegmentectomy (r = 0.91, P < 0.0001, n = 25). Five patients who had postoperative complications due to hepatic insufficiency (2 patients died of postoperative hepatic failure within 2 mo after operation) showed significantly lower predicted residual 99mTc-GSA clearance compared with the patients without complications (90.3 +/- 37.2 versus 320.9 +/- 158.8 mL/min; P < 0.005). CONCLUSION: The total hepatic 99mTC-GSA clearance reflected hepatic function. In addition, preoperative predicted residual hepatic 99mTc-GSA clearance was a good indicator of postoperative hepatic function and early prognosis. 99mTc-GSA dynamic SPECT is assumed to be a useful method for determining the surgical strategy in patients with hepatic tumor and especially in patients with hepatic dysfunction.

Coloring Agents↗
PubMed1999

Phase I and imaging trial of a monoclonal antibody directed against gastrin-releasing peptide in patients with lung cancer.

Small cell lung cancer (SCLC) cells express and secrete bombesin-like peptides (BLP) that can activate specific receptors that stimulate the growth of these cells. A murine monoclonal antibody, 2A11, which binds to the BLP, gastrin-releasing peptide with high affinity, has been reported to decrease the growth of SCLC cells in vitro and in athymic nude mice. A Phase I trial in lung cancer patients was performed using multiple doses of 2A11. Thirteen patients with lung cancer received 12 doses of 2A11 antibody three times a week for 4 weeks at one of four dose levels. Serum samples were obtained prior to initiation and before each dose of 2A11 antibody therapy for measurement of 2A11 antibody levels and determination of serum human anti-mouse antibody levels. A pilot imaging evaluation using 111In conjugated 2A11 monoclonal antibody was also performed in the same patients to aid in the study of pharmacokinetics and biodistribution. No toxic reactions were observed, and none of the patients developed detectable human antimouse antibody; however, no objective antitumor responses were observed. The mean trough serum 2A11 levels in patients increased with increasing dose level: 0.26+/-0.2 microg/ml, 6.7+/-6 microg/ml, 71.5+/-60 microg/ml, 248+/-184 microg/ml for dose levels 1 mg/m2, 10 mg/m2, 100 mg/m2, and 250 mg/m2, respectively. At each dose level, sustained detectable serum levels of the monoclonal antibody were achieved. Tumor uptake was noted in 11 of 12 patients who were injected with 111In conjugated 2A11. Because no dose-limiting clinical toxicity was observed, a mathematical model was used to define the recommended Phase II dose of 250 mg/m2. This trial established that repeated doses of monoclonal antibody 2A11 could be given safely to patients, and sustained levels could be achieved for a 4-week schedule. Further evaluation of the antitumor effects of 2A11 is warranted.

Animals↗