Systematic review and meta-analysis of the effect of meal intake on postprandial appetite-related gastrointestinal hormones in obese children.

UNLABELLED: Understanding the physiological response to meal intake, of gut-derived appetite and satiety hormone signals, in obese compared with healthy-weight children may assist with informing strategies to help curtail the obesity epidemic. A systematic review and meta-analysis of studies investigating the acute postprandial response of gastrointestinal appetite hormones to meal intake in obese children was undertaken. Systematic searches of databases EMBASE, CINAHL Plus, OVID Medline and the Cochrane Library were performed. INCLUSION CRITERIA: a randomised controlled trial or experimental cross-sectional study following an acute test meal protocol with pre- and postprandial analysis of plasma or serum gastrointestinal hormone concentrations. Database searching retrieved 1001 papers for review. Nine studies met the inclusion criteria, collectively reporting on six appetite hormones yielding a total of 32 test meal-hormone comparisons. Meta-analyses compared the pooled estimate of the mean difference of the postprandial change in total ghrelin and total peptide YY (PYY). Obese compared with healthy-weight children had an attenuated change in ghrelin at 60 min (N=5 studies; n=129 participants) and 120 min postprandial (N=4 studies; n=100 participants) (P<0.05 for both time points). Obese compared with healthy-weight children also had an attenuated PYY response at 60 min (N=5 studies; n=128 participants) and 120 min postprandial (N=4 studies; n=100 participants). Insufficient studies reported on the postprandial time course of other appetite-related hormones, precluding a meta-analysis. Limited evidence notwithstanding, these findings indicate that PYY and ghrelin responses to a meal may be altered in obese children. This review has also identified a major gap in knowledge of hormonal appetite responses in childhood obesity. More comprehensive investigations of the homoeostatic regulation of gut-derived appetite and satiety hormone signals with behavioural and clinical outcomes are warranted to understand if there are consequences of these differences.

The Nutritional Profile of Baby and Toddler Food Products Sold in Australian Supermarkets.

BACKGROUND/AIMS: To examine the nutritional profile of baby and toddler foods sold in Australia. METHODS: Nutrient information for baby and toddler foods available at Australian supermarkets was collected between Auguset and December 2013. Levels of declared energy, total fat, saturated fat, total sugar, sodium and estimated added sugar were examined, as well as the presence of additional micronutrients on the label. The Health Star Rating (HSR) system was used to determine nutritional quality. The range of products on offer was also examined by product type and by the age category for which the product was marketed. RESULTS: Of the 309 products included, 29% were fortified. On a per 100 g basis, these 309 products provided a mean (±SD) of 476 ± 486 kJ, 1.6 ± 2.4 g total fat, 10.7 ± 12.2 g total sugar, 2.7 ± 7.4 g added sugar, and 33.5 ± 66.5 mg sodium. Fruit-based products or products with fruit listed as an ingredient (58%) were the predominant product type. On the nutrition label, 42% displayed at least one additional micronutrient while 37% did not display saturated fat. The most common HSR was four stars (45%) and 6+ months was the most commonly identified targeted age group (36%). CONCLUSIONS: The majority of baby and toddler foods sold in Australian supermarkets are ready-made fruit-based products aimed at children under 12 months of age. Baby and toddler foods are overlooked in public policy discussions pertaining to population nutrient intake but their relatively high sugar content deriving from fruits requires close attention to ensure these foods do not replace other more nutrient dense foods, given children have an innate preference for sweet tastes.

A study of a pre-operative intervention in patients with diabetes undergoing cardiac surgery.

BACKGROUND: Coronary heart disease is common in Type 2 diabetes and often requires cardiac surgery. However poorer outcomes have been reported including increased rates of post-operative infection and prolonged hospital stay. AIM: The aim of the study was to determine the feasibility and acceptability of a specialist consultation model (pre-operative medical and educational intervention) for type 2 diabetes in the cardiac surgery setting. METHODS: Twenty four patients were assigned usual care or to the intervention group. The intervention group were assessed by a diabetes clinical nurse consultant, dietitian, and endocrinologist during a pre-operative visit. Specific diabetes questionnaires were administered, education was delivered, and protocol-driven changes to the medical regimen were instituted. Length of stay, incidence of post-operative complications, and number of post-operative inpatient review endocrinology visits required were recorded. RESULTS: Twenty four patients with a pre-operative HbA(1c) greater than 6.5% (48 mmol/mol) were studied (17 males and 7 females). In the usual care group (n = 15), HbA(1c) pre-operatively was 7.2% (55.2 mmol/mol) compared to 10.1% (86.9 mmol/mol) in the intervention group (n = 9). Six weeks post-operatively HbA(1c) fell significantly in the intervention group by 1.9% (to 8.2% [66.1 mmol/mol]) compared to a reduction of 1.2% (to 7.0% [53 mmol/mol]) in the usual care group (p < 0.05). No significant differences were observed in length of stay in intensive care or in total hospital stay between the groups: length of ICU stay 54 h for intervention versus 47 h for usual care, total hospital stay (mean 8 days for both); or in rates of post-operative infection. Differences were seen between in the diabetes questionnaires: in the Problem Areas in Diabetes questionnaire and in the Diabetes Treatment Satisfaction Questionnaire (p = 0.048). CONCLUSION: This small pilot feasibility study suggests there is potential benefit in the acute optimisation of diabetes treatment before elective cardiac surgery.

Plasma retinol: a novel marker for cardiovascular disease mortality in Australian adults.

BACKGROUND AND AIMS: Vitamin A affects inflammation and immune function and is thus a factor of interest in relation to cardiovascular disease (CVD). As vitamin A circulates in the plasma in the form of retinol, this study aims to describe the relationship between plasma retinol and the 5-year incidence of CVD mortality. METHODS AND RESULTS: Community-dwelling adults (n = 441, 45% with type 2 diabetes) were recruited in Melbourne, assessed at baseline and followed for 5 years. At baseline, CVD risk factors were assessed by clinical evaluation, by personal lifestyle questionnaire and from biochemistry (plasma fasting glucose, lipids, total homocysteine, C-reactive protein, retinol and carotenoids plus the urinary albumin excretion rate over 24 h.). Dietary intake was assessed by a validated food frequency questionnaire. CVD mortality over 5-years was determined by consulting state or national registries. The majority of participants had adequate plasma retinol concentrations (≥30 µg/dL). The final Cox regression model indicated that those in the highest tertile of plasma retinol (mean ± SD) 76 ± 14 µg/dL) had a significantly lower risk of 5-year CVD mortality (hazard ratio 0.27 [95% confidence interval 0.11, 0.68], P = 0.005), an effect that was not readily explained in terms of traditional CVD risk factors or dietary intake. CONCLUSION: In well-nourished older Australian adults, plasma retinol was inversely associated with CVD mortality via mechanisms apparently unrelated to established CVD risk factors and dietary intake.

Loss of secretion in mouse-human hybrids need not be due to the loss of a structural gene.

Three cloned mouse-human lines (B1-29, E2-42, and A2-31) secreting human immunoglobulin (Ig) were obtained from a fusion between the mouse myeloma line NS-1 and human tonsillar lymphocytes stimulated in vitro with pokeweed mitogen. One line, B1-29, has continued to secrete human IgG for a period of 2 yr in culture. This line was recloned three times to give a panel of secreting and nonsecreting subclones. Most of the nonsecreting subclones had also lost surface Ig. The structural genes for human Ig heavy chains have been provisionally assigned to chromosome 14, which also encodes the enzyme nucleoside phosphorylase. Human nucleoside phosphorylase was detected in all secreting and nonsecreting B1-29 subclones, indicating the presence of human chromosome 14. The retention of chromosome 14 in nonsecreting clones implied that the structural genes for human Ig were A2-31 and E2-42, which had stopped secreting, an attempt was made to restimulate the secreting of human Ig with mitogens A2-31 was unique among the cell lines examined, in that chromosome 14 could not be detected by an isoenzyme marker. Lipopolysaccharide, at an optimum dose of 10 micrograms/ml, restimulated these nonsecreting hybrid lines to secrete human IgG in levels up to 0.7 micrograms/ml. Loss of Ig secretion may not therefore be caused by loss of Ig structural genes.

A tumor-associated antigen specific for human kappa myeloma cells.

A monoclonal antibody (K-1-21) raised against a kappa Bence Jones protein exhibits unique binding properties to malignant plasma cells. K-1-21 is an IgG1 kappa antibody that reacts with human kappa light chains in free form, but shows no reactivity with heavy chain-associated kappa light chains. By immunofluorescence, K-1-21 binds to the surface of LICR LON/HMy2 (HMy2) kappa myeloma cells and to plasma cells from a majority (8/11) of patients with various types of kappa myeloma; it did not bind to the surface of normal cells, nor to malignant cells of non-kappa myeloma origin. Flow cytometry analysis of K-1-21 binding to HMy2 cells indicated that the surface reactivity of K-1-21 could be completely inhibited by preincubation of the antibody with purified kappa light chains, whereas no inhibition occurred after preincubation with lambda chains or intact human IgG. Thus, the epitope recognized by K-1-21 on the cell surface may be similar, if not identical, to the determinant recognized on soluble free kappa light chains, and constitutes a tumor-associated antigen with selectivity for kappa myeloma cells. K-1-21 may therefore have clinical potential in patients with kappa myeloma.

Measuring the success of an objective structured clinical examination for dietetic students.

BACKGROUND: Growing requirements to train more dietetic students greatly increase the teaching burden on clinical supervisors. This may be reduced if students can develop basic nutrition assessment skills before they commence clinical placement. To test achievement of these skills by Australian dietetic students, a preclinical objective structured clinical examination (OSCE) was developed. Performance at this OSCE was then compared with the performance at first clinical placement. METHODS: An OSCE was developed to test preclinical skills during the third year of a 4-year dietetic degree. Learning outcomes relating to nutritional assessment skills were assessed via a 1-h preclinical examination. Student application of these skills was then assessed after the first clinical placement, when performance was compared with the results at the preclinical OSCE. RESULTS: One hundred and ninety-three students completed the preclinical OSCE and first clinical placement during the period 2002-2007. A strong relationship was observed for individual student scores at the OSCE and the score achieved at the end of clinical placement (beta = 0.66; 95% confidence interval = 0.46-0.86; P < 0.0001). This relationship was maintained even when outliers were removed. No specific year effect was apparent. CONCLUSIONS: A third-year preclinical dietetic OSCE was found to be a valuable method of formative assessment for assisting dietetic students with the preparation for their first clinical placement. It aided the early identification of those students who are likely to do less well on their first clinical placement.

Diet and exercise in the prevention of diabetes.

BACKGROUND: Individuals with impaired fasting glucose or impaired glucose tolerance are at high risk of progression to type 2 diabetes. Lifestyle modification through change to diet and exercise habit has considerable potential to prevent or delay the onset of this disease. METHODS: A systematic literature search was undertaken of Medline, EMBASE, the Cochrane library and the Cumulative Index to Nursing and Allied Health Literature for journal articles relevant to the question of whether type 2 diabetes can be prevented by lifestyle change. RESULTS: Four cohort studies in a total of 4864 high risk individuals followed for a period of 2.5-6 years were identified. These showed that lifestyle change may reduce the incidence of type 2 diabetes by 28-59%. Moreover, follow-up studies also indicate that diabetes incidence rates continue to be depressed many years after the discontinuation of a lifestyle intervention. Evidence from a meta-analysis confirms this evidence and suggests that it would be necessary to treat 6.4 (95% confidence interval 5.0-8.4) individuals to prevent or delay one case of diabetes through lifestyle intervention. An examination of weight loss diets (low fat, high protein or Mediterranean) suggests each may be effective but each has limitations requiring care in food selection. Evidence also suggests that the maintenance of weight loss also requires regular exercise with an additional expenditure of approximately 8.4 MJ week(-1) (2000 kcal week(-1)). CONCLUSIONS: Diabetes can be prevented by lifestyle change. The challenge is to develop public health approaches to support individuals with respect to incorporating the lifestyle changes needed to reduce the risk of diabetes into their everyday life.

Thyroid allograft immunogenicity is reduced after a period in organ culture.

The survival time of mouse thyroid, transplanted under the kidney capsule of an H-2 incompatible recipient, is extended by holding the thyroid in organ culture for 12 days prior to transplantation.

The use of contextual learning to teach biochemistry to dietetic students.

This article describes the use of contextualized and "blended" learning to teach biochemistry to dietetic students during the second year of their professional training in a 4-year undergraduate degree (Bachelor of Nutrition and Dietetics). Contextualized content was used to engage students and motivate them to learn biochemistry, which many perceived as a "hard" subject. Contextualized learning presented via problem solving exercises, case-studies, and by the use of virtual subjects in laboratory class introduced content material through real life situations highly relevant to their later clinical practice. A "blended" curriculum where content was presented in a number of different modalities (on-line, on CD, or face-to-face in small/large groups and in tutorials/lectures/laboratory class) further enhanced contextualized learning by providing a range of learning modalities catering to different student learning styles. The on-line and CD material also allowed student self-assessment of learning progress through interactive quizzes in varied assessment formats, where feedback was often immediate. Student responses to this biochemistry course have been positive with 89% finding it intellectually stimulating.

Optimising the effectiveness of diabetes education in an East Asian population.

AIM: To explore the collective patterns of learning behaviours and preferences of Chinese people during diabetes education. The study was carried out across three countries and aimed to identify strategies that could be used to tailor diabetes education to Chinese people. METHODS: A case study approach was undertaken in three countries (Australia, China and Singapore) using participant observations and qualitative interviews. Purposive sampling was used to select field sites before a snowball technique was employed to identify relevant interviewees. Thematic analysis with pattern matching was used for data analysis. RESULTS: A total of 39 participant observations and 22 interviews were conducted. Chinese people with diabetes were observed seeking advice and recommendations from health professionals. When told clearly what to do, they strived for full compliance. They tended to be submissive during diabetes education and were not likely to raise concerns, negotiate or participate in making medical decisions. They appeared to prefer prescriptive concrete instructions rather than more flexible conceptual education and to believe that behavioural change should be achieved by individual willpower and determination, resulting in an 'all-or-nothing' approach. Regular repeated information sessions were reported to establish rapport and trust. CONCLUSIONS: For diabetes education to be culturally modified for Chinese people, there is a need to consider their unique philosophies and behaviours during education to support lifestyle changes. Building trust from the early stages of education was achieved by encouraging rapport through the provision of clear and precise instructions. This should be done before engaging in an open discussion of implementation strategies. Once the trust is built, healthy behaviour change may follow.

Dietary composition, body weight, and NIDDM. Comparison of high-fiber, high-carbohydrate, and modified-fat diets.

OBJECTIVE: To examine the effects of a high-carbohydrate low-fat (HCLF) and a modified-fat (MF) diet on body weight and metabolic control in subjects with non-insulin-dependent diabetes mellitus (NIDDM) living at home. RESEARCH DESIGN AND METHODS: Twenty-four NIDDM patients followed HCLF and MF diets alternately and in random order for a 3-month period while at home, with a 1-month baseline and washout between diets. Before and after each diet, fasting glucose and lipids, HbA1c, blood pressure, and body weight were measured. Dietary preferences were assessed by questionnaire. RESULTS: Subjects consumed 50% of energy as carbohydrate and 23% as fat on the HCLF diet and 40% of energy as carbohydrate and 36% as fat (over half of which was monounsaturated fat) on the MF diet. Subjects lost weight on both HCLF and MF diets (mean loss 0.7 and 1.3 kg, respectively). Although the MF diet resulted in a small decrease in fasting glucose levels, there was no significant change in HbA1c. Similarly, there was no significant difference between the diets in changes in blood pressure or fasting blood lipids. Most subjects (65%) preferred the MF diet. CONCLUSIONS: Although the MF diet is not a low-fat diet, it did not appear to facilitate weight gain in subjects with NIDDM living at home. The MF diet provides an alternative for individuals unable to comply with HCLF diets.

Effects of regular walking on cardiovascular risk factors and body composition in normoglycemic women and women with type 2 diabetes.

OBJECTIVE: To examine the impact of a 12-week walking program on body composition and risk factors for cardiovascular disease in women with type 2 diabetes and in normoglycemic women with first-degree diabetic relatives. RESEARCH DESIGN AND METHODS: There were 11 postmenopausal women with type 2 diabetes and 20 normoglycemic women of similar age and BMI who were asked to walk 1 h per day on 5 days each week for 12 weeks. Fitness (estimated VO2max) was assessed with a 1.6-km walking test; body composition was measured by dual-energy X-ray absorptiometry; and sex hormone, metabolic, and lipid concentrations were measured in serum. RESULTS: After 12 weeks, estimated VO2max improved in both groups (P < 0.005). In the diabetic women, BMI and fat content of the upper body and android waist region decreased (P < 0.05). Concentrations of fasting blood glucose (P < 0.05) HbAlc (P < 0.05), total cholesterol (P < 0.005), and LDL cholesterol (P < 0.05) decreased, while HDL cholesterol and sex hormones were unchanged. In contrast, normoglycemic women failed to lose body fat after 12 weeks of exercise in a walking program. However, their HbAlc, total cholesterol, LDL cholesterol, sex hormone-binding globulin, and total testosterone concentrations decreased (P < 0.05). On pooling the data and including diabetes as a categorical grouping variable, stepwise multiple regression analysis indicated that the change in centralized body fat, but not the change in VO2max, was related to change in fasting blood glucose. CONCLUSIONS: Twelve weeks of walking increased the fitness of diabetic and normoglycemic women. Improvement of fasting blood glucose was related to the loss of centralized body fat rather than to improved fitness.

Do postmenopausal women with NIDDM have a reduced capacity to deposit and conserve lower-body fat?

OBJECTIVE: To compare regional body fat distribution and sex hormone status of postmenopausal women with NIDDM with those of age- and BMI-matched normoglycemic women. RESEARCH DESIGN AND METHODS: The regional body fat distribution and sex hormone status of 42 postmenopausal women with NIDDM were compared with those of 42 normoglycemic women matched for age and BMI, who served as control subjects. Body composition was measured by dual-energy X-ray absorptiometry, and sex hormone-binding globulin (SHBG) and testosterone were measured in serum. RESULTS: Although the levels of total body fat were similar between the two groups, the women with NIDDM had significantly less lower-body fat (LBF) (P < 0.01) than the control subjects matched for age and BMI. This pattern of fat deposition in women with NIDDM was accompanied by an androgenic hormone profile, with decreased SHBG concentration and an increased free androgen index (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: A reduced capacity to deposit and/or conserve LBF may be an independent factor associated with (or may be a marker of) the metabolic manifestations of the insulin resistance syndrome in women with NIDDM. The possibility that the smaller relative accumulation of LBF is a consequence of the androgenic hormonal profile should be investigated in future studies.

Effect on serum lipids of monounsaturated oil and margarine in the diet of an Antarctic Expedition.

A 13-wk dietary intervention was carried out with 23 members of the 1991 wintering party of an Australian National Antarctic Research Expedition. Canola margarine and canola cooking oil were substituted for usual dietary fats (butter, a margarine containing 28% saturated fat, a polyunsaturated margarine, and vegetable oil). Mean energy intake slowly decreased although body weight slowly increased during the 42-wk wintering-over period. During 13 wk of dietary substitution, mean total cholesterol and low-density-lipoprotein-cholesterol concentrations fell by 7.0% and 10.0%, respectively (P < 0.05, repeated-measures ANOVA). These changes were not found in a second wintering-over group that did not experience this dietary intervention. The data indicate that a relatively simple change to the food supply has the potential to produce significant beneficial changes in lipoprotein lipid profile.

Arabinoxylan fiber, a byproduct of wheat flour processing, reduces the postprandial glucose response in normoglycemic subjects.

BACKGROUND: Arabinoxylan (AX) is the major component of dietary fiber in the cereal grains that make up a large proportion of our diet. However, the physiologic effect of AX is unknown. OBJECTIVE: The objective of this study was to determine whether AX improves postprandial glucose and insulin responses in healthy humans. DESIGN: AX-rich fiber was extracted from the byproduct of wheat-flour processing. Three isoenergic breakfasts, comprising bread, margarine, and jam, had 75 g available carbohydrate, 10 g protein, and 14 g fat and contained 0, 6, and 12 g AX-rich fiber, respectively. Fourteen healthy subjects consumed the 3 breakfast meals in random order on 3 mornings >/=3 d apart after an overnight fast. Blood was taken from the subjects at regular intervals over 2 h and was analyzed for glucose and insulin. The palatability of bread containing AX-rich fiber was compared with that of a control bread. RESULTS: Compared with the control meal containing 0 g AX-rich fiber, the peak postprandial glucose concentration after meals containing 6 and 12 g AX-rich fiber was significantly lower (6. 3 +/- 1.3 compared with 7.2 +/- 1.0 mmol/L, P < 0.01; 5.9 +/- 0.9 compared with 7.2 +/- 1.0 mmol/L, P < 0.001, respectively). The incremental area under the curve (IAUC) for glucose was 20.2% (95% CI: 5.8%, 34.7%; P < 0.01) and 41.4% (25.9%, 56.8%; P < 0.001) lower, whereas IAUC for insulin was 17.0% (2.0%, 32.1%; P < 0.05) and 32. 7% (18.8%, 46.6%; P < 0.001) lower, respectively. Bread containing AX-rich fiber was as pala as 50% whole-wheat bread when evaluated with sensory analysis by 30 volunteers. CONCLUSIONS: Postprandial glucose and insulin responses were improved by ingestion of AX-rich fiber. Further research is required to determine whether AX-rich fiber is of benefit to people with type 2 diabetes.

Modulation of fecal markers relevant to colon cancer risk: a high-starch Chinese diet did not generate expected beneficial changes relative to a Western-type diet.

In a randomized, crossover dietary intervention study, 12 Australians (of white descent) consumed a diet typical of low-income communities in China and an average Australian diet so that effects on fecal markers thought to be relevant to colon cancer risk could be compared. The Chinese diet contained 35.3 g starch/MJ daily [including 2 g resistant starch (RS)/MJ and 1.5 g nonstarch polysaccharides (NSPs)/MJ]; the Australian diet contained 12 g starch/MJ daily (including 0.8 g RS and 2.7 g NSPs/MJ). Subjects followed each diet for 3 wk. Serum cholesterol concentrations were significantly lower after the low-fat, high-starch Chinese diet than after the Australian diet (mean +/- SEM: 4.17 +/- 0.30 compared with 5.04 +/- 0.28 mmol/L, respectively, P < 0.05), a difference indicative of dietary compliance. Fecal pH was lower after the Chinese diet (6.51 +/- 0.04) than after the Australian diet (6.63 +/- 0.05; P < 0.05). For all other fecal markers examined, however, the Chinese diet produced less favorable changes, including lower fecal bulk (86 +/- 11 compared with 141 +/- 20 g wet wt/d, P < 0.01), slower transit through the gut (69 +/- 6 compared with 56 +/- 7 h, P = 0.06), lower fecal concentrations of short-chain fatty acids [72.8 +/- 7.3 compared with 98 +/- 7.6 mmol/L (including butyrate: 12.2 +/- 1.3 compared with 18.4 +/- 2.3 mmol/L), P < 0.05], and higher fecal concentrations of potentially damaging ammonia (540 +/- 50 compared with 450 +/- 40 mg/L, P < 0.01) and phenols (109.2 +/- 13.2 compared with 68.5 +/- 12.9 mg/L, P < 0.01). These results suggest that consumption of a high-starch diet alone is insufficient to reduce the risk of developing colon cancer.

Body fat distribution and non-insulin-dependent diabetes: comparison of a fiber-rich, high-carbohydrate, low-fat (23%) diet and a 35% fat diet high in monounsaturated fat.

The effects of a fiber-rich, high-carbohydrate, low-fat (HCLF) diet and a modified-fat (MF) diet high in monounsaturated fat on body fat distribution were examined by dual-energy X-ray absorptiometry (DXA) in 16 subjects with non-insulin-dependent diabetes (NIDDM) during a randomized crossover study. Subjects lost similar amounts of body fat consuming the HCLF and MF diets (-0.83 +/- 0.37 and -0.87 +/- 0.40 kg, respectively) despite a marked difference in total fat consumption. With the MF diet, the ratio of upper- to lower-body fat (UF:LF) remained unchanged because fat was lost proportionately from the upper and lower body. In contrast, with the HCLF diet, a disproportionate loss of lower-body fat caused the UF:LF to increase. The effects of diet on regional body fat loss were significant (P < 0.05, two-factor repeated-measures ANOVA).

Potentiation of hybridoma production by the use of mouse fibroblast conditioned media.

L-CM is a conditioned medium prepared from cultures of L-929 cells, a murine fibroblast line. It will promote the growth and antibody secretion of B cell hybridomas after fusion as well as facilitating cloning at limit dilution and the growth of cloned B cell lines in bulk culture. The medium is easy to prepare and stores well at 4 degrees C. It thus provides a convenient alternative to the use of feeder cells in the production of monoclonal antibodies.

Labeling of monoclonal antibodies with samarium-153 for combined radioimmunoscintigraphy and radioimmunotherapy.

The labeling of a monoclonal antibody K-1-21 with 153Sm has been investigated using the bifunctional chelate cyclic diethylenetriaminepentaacetic acid (DTPA) anhydride. Labeling efficiencies greater than 60% were obtained using high specific activity [153Sm]chloride and a cDTPAa:MAb conjugation ratio of 20:1. The resultant labeled antibody had a s.a. greater than 150 MBq.mg-1 and a % retained immunoreactivity greater than 90%. Imaging and biodistribution studies in a rat model demonstrated that specific uptake of 153Sm-K-1-21 into s.c. implants of the target antigen could be clearly detected in scintigrams at 6 days p.i. The specific uptake (1.90 +/- 0.45% ID/g, 19.95 +/- 2.20 Implant:Blood ratio) compared favorably to 131I- and 111In-labeled K-1-21 (2.52 +/- 0.20 and 3.33 +/- 0.20% ID/g, 7.69 +/- 0.45 and 10.10 +/- 0.60 I:B, respectively). Labeling of MAbs with 153Sm for combined scintigraphy/therapy is feasible at clinically appropriate specific activities using cDTPAa, with the resultant conjugates retaining immunoreactivity and in vivo antigen localization.