Epidural magnesium reduces postoperative analgesic requirement.

BACKGROUND: Magnesium has antinociceptive effects in animal and human models of pain. Our hypothesis was that the addition of magnesium to postoperative epidural infusion of fentanyl may decrease the need for fentanyl. METHODS: Fifty patients undergoing hip surgery were enrolled to receive either fentanyl (Group F) or fentanyl plus magnesium sulphate (Group FM) for 24 h for epidural analgesia. All patients were equipped with a patient-controlled epidural analgesia device and the initial settings of a demand bolus dose of fentanyl 25 microg. In Group FM, patients received 50 mg magnesium sulphate epidurally as an initial bolus dose followed by a continuous infusion of 100 mg day(-1). Ventilatory frequency, heart rate, blood pressure, pain assessment using a visual analogue scale (VAS), sedation scores and fentanyl consumption were recorded in the postoperative period. RESULTS: There was no significant difference between groups in the time to first analgesic requirement. Compared with Group F, patients in Group FM received smaller doses of epidural fentanyl (P < 0.05). The cumulative fentanyl consumption in 24 h was 437 (SD110) microg in Group F and 328 (121) microg in Group FM (P < 0.05). Patients in Group F showed a higher VAS score in the first hour of the postoperative period (P < 0.05). The groups were similar with respect to haemodynamic and respiratory variables, sedation, pruritus, and nausea. CONCLUSION: Co-administration of magnesium for postoperative epidural analgesia results in a reduction in fentanyl consumption without any side-effects.

Elevated levels of C-reactive protein are associated with impaired coronary collateral development.

BACKGROUND: In vitro studies have shown that C-reactive protein (CRP) attenuates nitric oxide production and inhibits angiogenesis, which may result in impaired collateral development. The aim of this study was to investigate the association between high sensitivity CRP (hsCRP) levels and the extent of coronary collaterals. MATERIALS AND METHODS: We investigated the association between hsCRP levels and the extent of coronary collaterals according to the Rentrop classification in a cohort of 185 patients who had high-grade coronary stenosis or occlusion on their angiograms. RESULTS: Mean age was 62 years and 80% were males. Subjects with a higher grade of collaterals were significantly less likely to have diabetes mellitus (OR; 0.48, 95% and CI; 0.28, 0.83) or acute coronary syndrome (OR; 0.58, 95% and CI; 0.33, 0.99), but they were more likely to have higher number of vessels with significant stenosis (OR; 1.41, 95% and CI; 1.03, 1.93) and to have received statins (OR; 1.84, 1.09, 3.13). The mean hsCRP values reduced significantly as the Rentrop grades increased (trend, P = 0.0006). After adjusting for age, gender, statin use, clinical presentation with acute coronary syndrome, diabetes mellitus and the number of vessels with significant stenosis, each 10-unit increase in hsCRP values corresponded to a 31% reduced odds of having a higher collateral score (OR; 0.69, 95% and CI; 0.53, 0.90). CONCLUSIONS: Our findings indicate that elevated hsCRP levels are associated with a significant impairment in coronary collateralization. These data suggest a previously unrecognized mechanism through which inflammation may worsen cardiovascular outcomes.

Antiangiogenic therapy with somatostatin receptor-mediated in situ radiation.

Tumor growth and the development of metastases require an angiogenic response. Angiogenic vessels uniquely express somatostatin subtype 2 (sst 2) receptors that can transport somatostatin or its analogs into the cell. We hypothesized that radiolabeled somatostatin analogs could inhibit the angiogenic response by selectively destroying proliferating endothelial cells. We evaluated the antiangiogenic effects of 111In-pentetreotide, an sst 2-preferring somatostatin analog in a human vessel model. Disks of human placental vein were embedded in fibrin gels in culture and observed for angiogenic sprouting for 14 days. Vein disks were treated with 111In-pentetreotide (1.5, 15, and 150 microCi/mL) on the day of implantation. Control groups included disks treated with nutrient medium alone, with 111In-chloride, and with unlabeled pentetreotide. The percentage of wells that initiated an angiogenic response and the overall length and density of neovessel sprouts were assessed on Day 14. 111In-pentetreotide treatment did not completely block initiation of the angiogenic response but significantly decreased the growth of neovessels after initiation. Both the receptor-specific Auger electron-induced and nonspecific gamma radiation-mediated effects contributed to the angiotoxicity.

Post-surgical ablation of thyroid remnants with high-dose (131)I in patients with differentiated thyroid carcinoma.

The aims of this study were to evaluate the efficacy of an empirically determined "fixed" high ablative dose of radioiodine ((131)I) therapy and to determine the utility of ultrasonography (US) in dose determination. A retrospective analysis was performed of 242 thyroid cancer cases treated with "fixed" high-dose (131)I for ablation of thyroid remnants without a pre-ablative (131)I diagnostic scintigraphy or radioiodine uptake study. Treatment doses ranged from 1850 MBq (50 mCi) to 7.4 GBq (200 mCi). The selection of the treatment dose was based on the surgical and pathological findings as well as the remnant thyroid volume calculated by US. A successful ablation was defined as the absence of activity in the thyroid bed on subsequent imaging studies. Successful ablation was obtained in 218 of the 242 patients (90%). In 162 of the 218 patients (74.3%), successful ablation was achieved after a single (131)I treatment. The remnant thyroid volume calculated by US was significantly different (P=0.04) between those who were successfully ablated and those who were not. The total (131)I dose needed for successful ablation was significantly higher in males (P=0.003). Patients with higher post-operative thyroglobulin (Tgb) levels and patients with a higher stage of disease required higher doses (P=0.036 and P=0.021 respectively). Serum Tgb levels were under 10 ng.ml(-1) in 220 of the 242 patients (90%) following radioiodine ablation while not receiving L-thyroxine suppression. Nineteen patients (7.8%) showed metastases on post-therapy scan and successful treatment was achieved in 11 of 19 (57.8%). Four of the 19 patients with distant metastases (revealed on post-treatment scan) were found to have been given a treatment dose of less than 200 mCi based on the proposed empirical approach. These results indicate that "fixed" high-dose (131)I treatment is clinically feasible with an acceptable dose underestimation rate, and the utilization of US in the determination of the thyroid remnant volume provides more accurate and reproducible results.

Clinical utility of frozen section in sentinel node biopsy in breast cancer.

One hundred sixty-five breast cancer patients underwent a sentinel lymph node biopsy procedure over a period of 2 years. Sentinel node (SN) could be successfully localized in 157 (95%) of the patients. Complete axillary lymph node dissection was performed only if the frozen section (FS) revealed a positive SN. All SN specimens were further evaluated by hematoxylin and eosin on multiple sections and cytokeratin immunohistochemisty. The patients whose SNs were negative by FS but positive by permanent histopathologic evaluation underwent a delayed axillary lymph node dissection. SN was positive in 41 of 157 (26%) patients. Eighteen (44%) of the 41 patients with SN metastases were diagnosed intraoperatively by FS and underwent a one-stage definitive surgical treatment. The benefit of FS was most notable in patients with T1c and larger lesions.

Antitumor and antiangiogenic effects of somatostatin receptor-targeted in situ radiation with (111)In-DTPA-JIC 2DL.

INTRODUCTION: Expression of somatostatin receptor subtype 2 (sst 2) in angiogenic tumor vessels appears to be homogeneous, while tumor cell expression of this receptor is often heterogeneous. We have developed a novel in vitro three-dimensional tumor angiogenesis model to study the antitumor and the antiangiogenic effects of radiolabeled somatostatin analogs. We hypothesized that targeted in situ radiation with an Auger electron-emitting radiolabeled somatostatin analog would produce receptor-specific cytotoxicity in sst 2-expressing cells. MATERIALS AND METHODS: IMR-32 human neuroblastoma (sst 2-positive) and MDA MB-231 human breast cancer (sst 2-negative) xenografts were created in nude mice from monolayer cell cultures. Fragments of these tumors were embedded in three-dimensional fibrin gels supplemented with endothelial growth media and incubated for a period of 14 days. Tumor fragments were treated with 50 microCi/ml of (111)In-JIC 2DL, a sst 2-preferring somatostatin analog, or medium on Day 1. Initial angiogenic activity was determined at 48 h and the mean angiogenic score and tumoricidal responses were assessed on Day 14. RESULTS AND CONCLUSION: Tumoricidal effects of (111)In-JIC 2DL were seen only in sst 2-positive IMR-32 tumors. However, the angiogenic response was inhibited in both IMR-32 and MDA MB-231 tumors independent of the tumor cells' sst 2 status. Somatostatin receptor-mediated in situ radiation therapy has profound cytotoxic effects on angiogenic blood vessels and sst 2-expressing tumor cells.

Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction.

BACKGROUND: Elevated plasma homocysteine level is an independent risk factor for cardiovascular disease. A common mutation (nucleotid 677C-T) in the gene coding for methylenetetrahydrofolate reductase (MTHFR) has been reported to reduce the enzymatic activity of MTHFR and is associated with elevated plasma levels of homocysteine, especially in subjects with low folate intake. HYPOTHESIS: Methylenetetrahydrofolate reductase T/T genotype may be a risk factor for premature MI in Turkish population who are known to have low folate levels. METHODS: The study group was comprised of 96 men (aged <45 years) with premature myocardial infarction (MI) and 100 age- and gender-matched controls who had no history or clinical evidence of coronary artery disease (CAD) and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. RESULTS: Allele and genotype frequencies among cases and control subjects were compatible with Hardy-Weinberg equilibrium. The frequencies of T/T, C/T, and C/C genotypes among patients with MI and control subjects were 15.6, 40.6, and 43.8%, and 5, 35, and 60%, respectively. Multivariate analyses identified smoking, MTHFR C/T polymorphism, diabetes mellitus, family history of CAD, and hypertension as the independent predictors of premature MI. Defining patients with non-T/T genotype (C/C and C/T combined) as reference, the relative risk of MI for subjects with T/T genotype was 5.94 (95% confidence interval: 1.96-18.02, p = 0.0016). CONCLUSIONS: Our findings suggest that C677T transition in the MTHFR gene may be a risk factor for premature MI in Turkish men.

Hyperhomocysteinemia and restenosis.

OBJECTIVE: This study was undertaken to assess the effect of plasma homocysteine level on angiographic restenosis 6 months after coronary angioplasty. METHODS: The plasma homocysteine level was measured in 100 consecutive patients at the time of coronary angioplasty, 56 patients who attended a 6-month follow-up angiogram being enrolled to the study; the 44 patients without a control coronary angiogram were not enrolled. Patients with and without angiographic restenosis were designated as groups A (n = 34) and B (n = 22) respectively. RESULTS: The baseline demographic (groups A and B), angiographic (groups A and B) and procedural characteristics were similar in both groups. The mean plasma homocysteine level (SD) was 15.2 (7.7) and 11.1 (2.5) mumol/l in groups A and B respectively (P = 0.007; 95% CI -6.9 to -1.1). With respect to the plasma homocysteine level, the upper and the lower thirds were compared by binary logistic regression (the lower third homocysteine level being < 10.6 mumol/l and the upper third homocysteine level > 14.1 mumol/l). The angiographic restenosis rate for the lower and upper tertiles was 47.4% and 89.5% respectively (P = 0.01; OR = 9.4; 95% CI 1.6-52.7). After adjustment for age and sex, the statistical significance did not change (P = 0.013; OR = 9.43; 95% CI 1.6-54.9). Even after adjustment for age, sex, smoking, hypertension, hypercholesterolemia, and diabetes mellitus, there was a statistically significant difference between the upper and lower tertiles (P = 0.008; OR = 41.3; 95% CI 2.6-635). CONCLUSION: Increased plasma homocysteine level and diabetes mellitus were independent risk factors for angiographic restenosis after percutaneous transluminal coronary angioplasty and coronary stenting.

Non-hindbrain-related syringomyelia. Obstruction of the subarachnoid space and the central canal in rats. An experimental study.

BACKGROUND: The aim is to determine the mechanism of non-hindbrain-related syringomyelia in experimental models. The effects of obstruction of central canal and subarachnoid space on occurrence of cavities were discussed. METHODS: 31 Sprague-Dawley rats were used with eight (Group D) as a control. In 10 rats (Group A) 1.5 microl kaolin was microinjected into the dorsal columns and central gray matter of the spinal cord at the level of Th6-10. In 10 rats (Group B) 0.1 cc kaolin was injected into the subarachnoid space at the same level. In 3 rats (Group C), 1.5 microl kaolin was administered into both dorsal midline of the spinal cord and the subarachnoid space. RESULTS: In Group A, histological examination revealed cystic cavity and dilatation of the central canal in five rats; denuded ependymal line and multicystic formations in ependymal and periependymal areas in seven rats. In Group B, denuded ependymal line in three rats and microcystic formations in ependymal and periependymal areas in four rats were revealed. In Group C, there were microcystic formations in two rats and syrinx cavity in one rat. CONCLUSIONS: Developments leading to occurrence of cavities are focused on the central canal in all groups. These models indicate that the CSF-flow is from the subarachnoid space to the central canal leading to changes of cavities. In cases of obstruction of the subarachnoid space or the central canal, the occurrence of syrinx cavity initially is due to increased CSF (cerebrospinal fluid) pressure in the central canal. Flow changes in spinal cord is indicated by this study.

Bronchial hyperreactivity in patients with mitral stenosis before and after successful percutaneous mitral balloon valvulotomy.

OBJECTIVES: We aimed to identify the bronchial response to inhaled methacholine in patients with mitral stenosis (MS) and to clarify whether or not the bronchial hyperreactivity (BHR) is reversible after percutaneous mitral balloon valvulotomy (PBMV). PATIENTS AND SETTING: Thirty patients with MS and 28 age-matched healthy control subjects were prospectively evaluated with pulmonary function tests and methacholine challenge. The productive concentration of methacholine causing 20% decrease in FEV(1) (PC(20)) was calculated and used as a parameter of bronchial responsiveness. BHR was defined as a PC(20) < 8 mg/mL. Mean pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) were recorded in all patients through a Swan-Ganz balloon-tipped catheter. Sixteen patients underwent PMBV, and a methacholine test was repeated after each procedure. RESULTS: Bronchial response to methacholine was significantly increased in patients with MS, so that 53% of them had BHR, whereas all control subjects were nonresponders. The PC(20) was closely correlated with the PAP (r = - 0.777; p < 0.001), PCWP (r = - 0.723; p < 0.001), and mitral valve area (MVA; r = 0.676; p < 0. 001). Balloon valvulotomy was successfully performed in all of the 16 patients, and the cardiac parameters (MVA, PAP, and PCWP) significantly improved after the procedure. In contrast, no significant changes were shown in pulmonary function test variables (total lung capacity, vital capacity [VC], FEV(1), and FEV(1)/VC). Although significant improvement was observed in the mean PC(20) values (from 4.97 +/- 5.24 to 7.47 +/- 6.96 mg/mL; p = 0.0006), BHR was completely eliminated in only one patient. CONCLUSIONS: Our data shows that BHR is fairly common among patients with MS, and severity of bronchial responsiveness is significantly correlated with the severity of MS. Moreover, PMBV leads to significant reduction in pulmonary congestion and a consequent improvement in BHR.

A thousand points of light or just dim bulbs? Radiolabeled antibodies and colorectal cancer imaging.

Radioimmunoscintigraphy (RIS) is coming into its own as an imaging modality in clinical oncology. Early experience with indium-111-labeled intact murine monoclonal antibodies (MoAbs) in colorectal cancer suggested that RIS images hepatic metastases poorly. Moreover, an antimurine immune response was frequently provoked, precluding multiple follow-up RIS studies in individual patients due to reticuloendothelial sequestration of the radioimmunoconjugate before tumor targeting could occur. Recent trials of technetium-99m-labeled antibody fragments and human MoAbs have demonstrated significant improvement in imaging efficacy, and repeated or serial imaging is possible because of the absence of associated immunogenicity. RIS is demonstrably more sensitive than conventional diagnostic modalities (CDM) such as computed tomography (CT) for detection of extrahepatic abdominal and pelvic colorectal carcinoma and is complementary to CDM in imaging liver metastases. In a surgical decision-making analysis comparing CT, RIS (IMMU-4 99mTc-Fab'; CEA-Scan), and CT plus RIS in patients with recurrent or metastatic colorectal cancer, CT plus RIS improved correct prediction of resectability by 40% and correct prediction of unresectability by 100% compared with CT alone. At the present time, RIS used in combination with CDM contributes an incremental improvement in diagnostic accuracy in colorectal cancer patients with known or suspected recurrent disease. Basic and clinical research currently in progress promises to yield agents and methods that provide rapid high-resolution imaging, high tumor-to-background ratios in all organs at risk for tumor recurrence or metastasis, negligible immunogenicity and toxicity, and a significant further improvement in the accuracy of clinical decision making in oncology patients.

Unfiltered sulfur colloid and sentinel node biopsy for breast cancer: technical and kinetic considerations.

BACKGROUND: There are few clinical data on technical limitations and radiocolloid kinetics related to sentinel lymph node (SLN) biopsy for breast cancer. METHODS: In 70 clinical node-negative patients, unfiltered 99mTc sulfur-colloid was injected peritumorally and cutaneous hot spots were mapped with a gamma probe. SLN biopsy was performed followed by axillary lymph node dissection. Missed radioactive nodes (nodes not under hot spots) were removed from axillary lymph node dissection specimens and submitted separately. RESULTS: At least one hot spot was mapped in 69 patients (98%) and SLNs were retrieved in 62 (89%). No radiolabeled nodes were found in five (7%) and only nodes not under hot spots were retrieved in three patients (4%). Residual nodes not under hot spots were retrieved in 17 patients (24%) in whom at least one SLN specimen had been found. Diffuse radioactivity around the radiocolloid injection site impeded identification of all radiolabeled nodes during SLN biopsy, and was responsible for one of two false negatives (20 node-positive patients; false-negative rate 10%). Hot spot radioactivity, number of radiolabeled nodes, and nodal radioactivity did not change with time interval from radiocolloid injection to surgery (0.75-6.25 hours). CONCLUSIONS: Although SLN localization rate is high, intraparenchymal injection may predispose to failure of radiocolloid migration, failure to identify SLNs because of high radiation background, and false-negative outcomes. Alternative routes of radiocolloid administration should be explored.

Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma.

This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 1311I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single-photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were > or =2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade > or =3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were > or =2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.

Sentinel lymph node localization in early breast cancer.

METHODS: Thirty-two patients with clinical node-negative breast cancer underwent sentinel node localization study as part of a National Cancer Institute-sponsored multicenter trial. Anatomical and histopathologic characteristics of sentinel lymph node (SLN) and a kinetic analysis of nodal uptake were studied. Patients were injected with 1 mCi/4 ml unfiltered 99mTc-sulfur colloid in four divided doses around the palpable lesion or immediately adjacent to the excision cavity if prior biopsy was performed. SLN biopsy was performed 1.5-6 hr (mean = 3 hr) postinjection. Intraoperative localization was performed using a gamma probe. All patients underwent complete axillary dissection. RESULTS: SLN was identified in 30 of 32 (94%) patients. There were no false-negative SLN biopsies. CONCLUSION: This study supports the clinical validity of SLN biopsy in breast cancer and confirms that, unlike the blue dye technique, the learning curve with unfiltered 99mTc-sulfur colloid and the gamma detection probe is short, and SLN localization is achievable in over 90% of cases by surgeons with modest experience. The use of unfiltered 99mTc-sulfur colloid (larger particle size) with larger injected volume permits effective localization of SLNs.

Comparison of caudal bupivacaine, bupivacaine-morphine and bupivacaine-midazolam mixtures for post-operative analgesia in children.

Sixty children undergoing inguinal or urogenital surgery were allocated randomly to three groups to receive a caudal injection of either 0.125% bupivacaine 0.75 mL kg-1 with 0.5% midazolam 50 micrograms kg-1 (n = 20) or with 1% morphine chlorhydrate 0.05 mg kg-1 (n = 20), or bupivacaine alone (n = 20) after surgery under general anaesthesia. There were no significant changes in heart rate, blood pressure, respiratory rate or oxygen haemoglobin saturation values in all groups, and there were no significant differences in the incidence of vomiting and pruritus between the groups (P > 0.05). Sedation scores were higher in the bupivacaine-midazolam and the bupivacaine-morphine groups than in the bupivacaine group at 8-12 h post-operatively (P < 0.01). The durations of analgesia were 21.15 +/- 1.2 h in the bupivacaine-midazolam group, 14.50 +/- 1.6 h in the bupivacaine-morphine group and 8.15 +/- 1.3 h in the bupivacaine group. Differences between the bupivacaine-midazolam group and the bupivacaine group (P < 0.001), the bupivacaine-midazolam group and the bupivacaine-morphine group (P < 0.01), and the bupivacaine-morphine group and the bupivacaine group (P < 0.01) were significant. It is suggested that caudal administration of a bupivacaine-midazolam mixture produces a longer duration of post-operative analgesia than a bupivacaine-morphine mixture and bupivacaine alone with sedation for 8-12 h post-operatively.

Somatostatin receptor expression in Hürthle cell cancer of the thyroid.

Somatostatin receptor expression, which was not a previously described marker for Hürthle cell cancer of the thyroid, was demonstrated by in vivo imaging with (111)In-pentetreotide in three patients. This phenomenon not only adds another imaging technique to the nuclear medicine armamentarium for detecting recurrent and metastatic cancer in patients with Hürthle cell cancer but also opens up an alternative therapeutic avenue with somatostatin analogs or their radiolabeled compounds.

Gamma probe guided sentinel node biopsy in breast cancer.

Axillary lymph node status is the most important pathological determinant of prognosis in early breast cancer. Determination of axillary status is crucial in clinical decision-making. It is currently accepted that the total axillary lymphadenectomy is the most reliable staging procedure. However, routine axillary dissection does not benefit a majority of early breast cancer patients who are node-negative, and the patients sustain the potential morbidity and the economic cost of this procedure. There is substantial evidence that there is an orderly progression of breast cancer metastases in a lymphatic basin, sentinel node being the first node to receive lymphatic drainage from the tumor site. Sentinel lymph node biopsy may prove to be the optimal sampling technique for staging of breast cancer patients. A large multicenter trial to study the clinical validity of sentinel lymph node biopsy in breast cancer is underway. This paper addresses the rationale for sentinel lymph node biopsy and discusses the technical issues with regard to anatomy and physiology of breast lymphatics.

Pilot radioimmunotherapy trial with 131I-labeled murine monoclonal antibody CC49 and deoxyspergualin in metastatic colon carcinoma.

An antimouse immune response is invariable following administration of murine monoclonal antibody (mAb), precluding effective multidose therapy. In advanced colorectal cancer patients, we carried out a pilot study with multiple doses of 131I-labeled CC49 administered with deoxyspergualin (DSG), an immunomodulator, to determine its effect on immune response. Cumulative toxicity and efficacy were also evaluated. Six patients with tumor-associated glycoprotein 72-expressing colorectal cancer were treated i.v. with 15 mCi/m2 131I-labeled to 20 mg mAb CC49 biweekly, along with concurrent DSG 200 mg/m2 daily for 5 days, for a maximum of four courses. None had received prior murine mAbs. All patients had targeting of radioactivity to known tumor sites following initial infusion. Four of six patients received all four courses of therapy, three without any acute side effects. In these patients, there was no change in serum clearance with variable tumor targeting following repeat infusions. Two patients had

Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.