Neonatal outcomes following planned preterm delivery in diabetic mothers.

OBJECTIVE: Women with diabetes may need elective preterm delivery due to pregnancy or diabetes related complications. The aim of this study was to describe the neonatal outcomes arising from elective preterm delivery in diabetic women. METHOD: Suitable patients were identified by the obstetric team at Hull Royal Infirmary Women and Children's Hospital and data was extracted from their case notes. 45 diabetic women with planned preterm delivery were identified within a set time frame, resulting in 48 babies. RESULTS: Of the 48 babies born, 47 survived. 36 out of 48 were delivered via caesarean section. Gestational ages ranged from 29+3 to 36+6 weeks, and 24 out of 48 (50%) had a birth weight greater than the 90th centile for gestational age.34 out of the 48 babies experienced some form of neonatal complication and were admitted to the neonatal unit. The median duration of stay in the neonatal unit was 7 days. 14 of the surviving neonates suffered from respiratory distress, although only 4 required surfactant therapy to regain respiratory function. However, the incidence of serious neonatal complications in those born after 34 weeks was shown to be low. CONCLUSIONS: Elective preterm delivery after 34 weeks had little effect on overall neonatal outcome. Therefore it could be proposed that elective preterm delivery after 34 weeks gestation may be an acceptable option in diabetic women if there are maternal or obstetric complications.

Perceptions of underweight images: are women with anorexia nervosa perceived as attractive and healthy?

The current study examined the impact of receiving information about a woman's eating disorder status on perceptions of the woman's health and attractiveness. A total of 99 females and 84 males viewed a photo of a model who had disclosed her diagnosis of anorexia nervosa. Participants were randomly divided into three groups: model (M) group (those who were informed that the photo showed a model), eating disorders (ED) group (those who were informed that the photo showed a woman with an eating disorder), and no description control (C) group. Male and female participants in the ED group rated the woman in the photo as less healthy than did participants in the M and C groups. However, there were no differences between groups for ratings of attractiveness or the participants' desire to achieve a similar look (for females). Additionally, male participants rated the photo as less attractive than female participants had predicted. Finally, internalization of the thin ideal was a significant predictor of ratings of health and attractiveness of the woman in the photo.

Estimation of lean body weight in older women with hip fracture.

OBJECTIVE: Lean body weight (LBW) decreases with age while total body fat increases, resulting in altered drug pharmacokinetics. A semi-mechanistic equation estimating LBW using height, weight and sex has been developed for potential use across a wide range of body compositions. The aim of this study was to determine the ability of the LBW equation to estimate dual energy x-ray absorptiometry-derived fat free mass (FFM(DXA)) in a population of older women with recent hip fracture. METHODS: Baseline, four and 12 month data obtained from 23 women enrolled in the Sarcopenia and Hip Fracture study were pooled to give 58 measurements. LBW was estimated using the equation: LBW (kg) = (9270 x Wt) / (8780 + (244 x BMI)). Body composition was classified as: 'normal' (BMI <25kg/m(2) and not sarcopenic), 'overweight-obese' (BMI >25kg/m(2) and not sarcopenic), 'sarcopenic' (sarcopenic and BMI <25kg/m(2)), or 'sarcopenic-obese' (sarcopenic and BMI >25kg/m(2)). The ability of the LBW equation to predict FFMDXA was determined graphically using Bland-Altman plots and quantitatively using the method of Sheiner and Beal. RESULTS: The mean ± SD age of female participants women was 83±7 years (n=23). Sarcopenia was frequently observed (65.2%). Bland-Altman plots demonstrated an underestimation by the LBW equation compared to FFMDXA. The bias (95% CI) and precision (95% CI) calculated using the method of Sheiner and Beal was 0.5kg (-0.7, 1.66kg) and 4.4kg (-3.7, 12.4kg) respectively for pooled data. CONCLUSION: This equation can be used to easily calculate LBW. When compared to FFMDXA, the LBW equation resulted in a small underestimation on average in this population of women with recent hip fracture. The degree of bias may not be clinically important although further studies of larger heterogeneous cohorts are needed to investigate and potentially improve the accuracy of this predictive equation in larger clinical cohorts.

Neuropsychological functioning in a young adult case of schizencephaly.

Schizencephaly is a rare neuromigrational/organizational disorder characterized by the development of cerebral clefts, which are typically associated with neurological sequelae including seizures, motor disturbances, and cognitive dysfunction. Although there are multiple case reports of schizencephaly and associated neurological sequelae, primarily in children, the literature regarding neuropsychological manifestations of schizencephaly is limited. This article reviews the case of a woman diagnosed with bilateral schizencephaly at age 29. Neuropsychological testing revealed intact intelligence and memory functioning. However, impairments were noted in attention, executive functioning, expressive language skills, visual-spatial abilities, and bilateral manual motor skills, all of which were adversely impacting her functional abilities (e.g., ability to be gainfully employed). Given the potential variability in deficits associated with schizencephaly, this case demonstrates the utility of neuropsychological evaluation for understanding cognitive and functional consequences of bilateral schizencephaly.

Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

The increasing application of Ac-225 for cancer therapy indicates the potential need for its increased production and availability. The production of Ac-225 has been achieved using bremsstrahlung photons from an 18 MV medical linear accelerator (linac) to bombard a Ra-226 target. A linac dose of 2800 Gy produced about 64 microCi of Ra-225, which decays to Ac-225. This result, while consistent with the theoretical calculations, is far too low to be of practical use. A more powerful linac is required that runs at a higher current, longer pulse length and higher frequency for practical production. This process could also lead to the reduction of the nuclear waste product Ra-226.

A theoretical model for the production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation on a small scale by bombarding Ra-226 with high-energy photons from a medical linear accelerator (linac) to produce Ra-225, which subsequently decays to Ac-225, which can be used as a generator to produce Bi-213 for use in 'targeted alpha therapy' for cancer. This paper examines the possibility of producing Ac-225 with a linac using an accurate theoretical model in which the bremsstrahlung photon spectrum at 18 MV linac electron energy is convoluted with the corresponding photonuclear cross sections of Ra-226. The total integrated yield can then be obtained and is compared with a computer simulation. This study shows that at 18 MV, the photonuclear reaction on Ra-226 can produce low activities of Ac-225 with a linac. However, a high power linac with high current, pulse length and frequency is needed to produce practical amounts of Ac-225 and a useful reduction of Ra-226.

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by (213)Bi-C595 radioimmunoconjugate.

Control of micrometastatic pancreatic cancer remains a major objective in pancreatic cancer treatment. The overexpression of MUC1 mucin plays an important role in cancer metastasis. The aim of this study was to detect the expression of MUC1 in human primary tumour tissues and three pancreatic cancer cell lines (CAPAN-1, CFPAC-1 and PANC-1), and target MUC1-positive cancer cells in vitro using (213)Bi-C595 alpha-immunoconjugate (AIC). The expression of MUC1 on pancreatic tumour tissues and cancer cell lines was performed by immunohistochemistry and further confirmed by confocal microscope and flow cytometry analysis on the cell surface. Cytotoxicity of (213)Bi-C595 was tested by MTS assay. Apoptosis was documented using TUNEL assay. Overexpression of MUC1 was found in approximately 90% of tested tumour samples and the three pancreatic cancer cell lines. (213)Bi-C595 is specifically cytotoxic to pancreatic cancer cells in a concentration-dependent fashion. These results suggest that overexpression of MUC1 in pancreatic cancer is a useful target, and that the novel (213)Bi-C595 AIC selectively targets pancreatic cancer cells in vitro. (213)Bi-C595 may be a useful agent for the treatment of micrometastases or minimal residual disease (MRD) in pancreatic cancer patients with overexpression of MUC1 antigen.

Effects of 20-mg oestradiol implant therapy on bone mineral density, fat distribution and muscle mass in postmenopausal women.

This 64-week prospective cohort trial evaluated the effects of 20-mg oestradiol implants, replaced every 4 months, in healthy postmenopausal women aged 45-65 years. Of 20 implant and 14 control subjects who remained in the trial at 32 weeks, 13 implant and seven controls continued to 64 weeks, with no baseline differences between completing and dropout subjects. At 64 weeks, implant subjects displayed increases of 5.4-7.6% in spine and hip bone mineral density ( p<0.05 versus controls). The abdominal fat-to-lean soft tissue ratio decreased by 18% in implant subjects ( p<0.001), but did not change in controls ( p<0.05 implants versus controls). Neither group displayed significant changes in weight, %fat or appendicular skeletal muscle mass. The 32-week data were consistent with these results. Hence, oestradiol implant therapy can reduce abdominal adiposity and could lower the risk of obesity-related metabolic disorders.

Body composition of Aboriginal Australian women: comparison with age-matched Caucasians.

Although Aboriginal Australians (AA) exhibit an android fat deposition profile and suffer from a high incidence of type 2 diabetes, a comprehensive body composition assessment of AA has not yet been reported. The body composition of 16 non-diabetic AA women and 16 healthy age- and weight-matched Caucasian women (C) showed no significant ethnic differences in height, total body bone mineral density, total and appendicular skeletal muscle mass, and % fat. The abdominal fat-to-lean soft tissue ratio correlated more highly with age in AA ( r=0.79, p<0.001) than in C ( r=0.59, p<0.05) and with % fat in AA ( r=0.67, p<0.01) than in C ( r=0.54, p<0.05). However, analysis of variance showed that the difference between the two ethnic groups was not significant. Key findings are that dual-energy X-ray absorptiometry can accurately assess adiposity, and that hip girth should emerge as a valid predictor of central adiposity, in AA women.

Human uveal melanoma expresses NG2 immunoreactivity.

BACKGROUND/AIMS: NG2 is the rat homologue of the human melanoma proteoglycan (HMP), also known as the high molecular weight melanoma associated antigen. Most cutaneous melanomas, as well as glioblastomas, chondrosarcomas, and some leukaemias express NG2 immunoreactivity, recognised using monoclonal antibody (mAb) 9.2.27. This antibody has also been used for molecular targeting in targeted alpha therapy for melanoma. The purpose of this study was to evaluate the expression of NG2 immunoreactivity in human uveal melanoma and normal ocular tissue using mAb 9.2.27. METHODS: Enucleated eyes from 26 patients with choroidal or ciliary body melanoma (n=26) were available as paraffin sections, and stained with haematoxylin and eosin to assess for tumour cell type and histopathology. Additional slides were investigated for NG2 immunoreactivity using mAb 9.2.27 and alkaline phosphatase anti-alkaline phosphatase (APAAP) immunostaining. Two independent observers graded immunostaining using a semiquantitative scale from 0 (negative) to 3 (strong). RESULTS: Immunostaining for mAb 9.2.27 could not be graded in 7/26 cases with dense pigmentation of the tumour. For the remaining cases, grade 2 (moderate) or more immunostaining was seen in 18/19 tumours (95%). The retina, retinal pigment epithelium (RPE), and choroid displayed weak immunostaining (grade 0.5-1.5) in the majority of melanoma affected eyes. Normal retina and choroid (n=5) appeared negative for mAb 9.2.27. Optic nerve axon bundles in both control and melanoma affected eyes displayed moderate immunostaining. CONCLUSION: In the present study, the majority of human uveal melanomas expressed NG2 immunoreactivity, as detected using mAb 9.2.27. This antibody may be a suitable candidate for radioimmunotherapy to target ocular melanoma.

Preclinical studies of targeted alpha therapy for breast cancer using 213Bi-labelled-plasminogen activator inhibitor type 2.

The control of micrometastatic breast cancer remains problematic. To this end, we are developing a new adjuvant therapy based on (213)Bi-PAI2, in which an alpha-emitting nuclide ((213)Bi) is chelated to the plasminogen activator inhibitor-2 (PAI2). PAI2 targets the cell-surface receptor bound urokinase plasminogen activator (uPA), which is involved with the metastatic spread of cancer cells. We have successfully labelled and tested recombinant human PAI2 with the alpha radioisotope (213)Bi to produce (213)Bi-PAI2, which is highly cytotoxic towards breast cancer cell lines. In this study, the 2-day postinoculation model, using MDA-MB-231 breast cancer cells, was shown to be representative of micrometastatic disease. Our in vivo efficacy experiments show that a single local injection of (213)Bi-PAI2 can completely inhibit the growth of tumour at 2 days postcell inoculation, and a single systemic (i.p.) administration at 2 days causes tumour growth inhibition in a dose-dependent manner. The specific role of uPA as the target for (213)Bi-PAI2 therapy was determined by PAI2 pretreatment blocking studies. In vivo toxicity studies in nude mice indicate that up to 100 microCi of (213)Bi-PAI2 is well tolerated. Thus, (213)Bi-PAI2 is successful in targeting isolated breast cancer cells and preangiogenic cell clusters. These results indicate the promising potential of (213)Bi-PAI2 as a novel therapeutic agent for micrometastatic breast cancer.

Solid state microdosimetry in hadron therapy.

A report of recent developments in silicon microdosimetry is presented. SOI based microdosemeters have shown promise as a viable alternative to traditional tissue-equivalent proportional counters. The application of these silicon microdosemeters to such radiation therapy modalities as boron neutron capture therapy (BNCT), boron neutron capture synovectomy (BNCS), proton therapy (PT), and fast neutron therapy (FNT) has been performed. Several shortcomings of the current silicon microdosemeter were identified and will be taken into account in the design of a second-generation device.

In vitro studies of gadolinium-DTPA conjugated with monoclonal antibodies as cancer-specific magnetic resonance imaging contrast agents.

The monoclonal antibodies, 9.2.27 against human melanoma cell lines and WM53 against leukemia cell lines, were conjugated with cyclic anhydride gadolinium-diethylenetriaminepenta-acetic acid (Gd-cDTPAa) and used as tumor-specific contrast agents in magnetic resonance imaging (MRI). The data indicate that Gd-DTPA-9.2.27 in solution decreased the T1 relaxation of water protons at 7.0 Tesla (300 MHz) in direct proportion to the gadolinium concentration, and this effect was greater than in Gd-DTPA solutions. These conjugates show high specificity for melanoma and leukemia cell lines. T1 relaxation time at 7.0 Tesla, measured for the melanoma cell line (MM-138) and leukemia cell line (HL-60) after incubation at 37 degrees C for 4 hr, were significantly decreased (approximately 25%) relative to controls. The gadolinium concentration in cells and washing solutions was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES). A linear relationship was observed between T1 relaxation rates and gadolinium concentrations obtained by ICP-AES. The ICP-AES results showed no gadolinium uptake in the non-targeted HT-29 colorectal cancer cells.

213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model.

A novel alpha-particle emitting ((213)Bi) plasminogen activator inhibitor type 2 construct, which targets the membrane-bound urokinase plasminogen activator on prostate cancer cells, was prepared and evaluated in vitro and in a xenograft animal model. The PC3 prostate cancer cell line expresses urokinase plasminogen activator which binds to its receptor on the cell membrane; plasminogen activator inhibitor type 2 is bound to urokinase plasminogen activator/urokinase plasminogen activator receptor to form stable complexes. In vitro, the cytotoxicity of (213)Bi-plasminogen activator inhibitor type 2 against prostate cancer cells was tested using the MTS assay and apoptosis was documented using terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labelling (TUNEL) assay. In vivo, antiproliferative effects for tumours and prostate cancer lymph node metastasis were carried out in an athymic nude mouse model with a subcutaneous xenograft of PC3 cells. (213)Bi-plasminogen activator inhibitor type 2 was specifically cytotoxic to PC3 cells in a concentration-dependent fashion, causing the cells to undergo apoptosis. A single local or i.p. injection of (213)Bi-plasminogen activator inhibitor type 2 was able to completely regress the growth of tumours and lymph node metastases 2 days post subcutaneous inoculation, and obvious tumour regression was achieved in the therapy groups compared with control groups with (213)Bi-plasminogen activator inhibitor type 2 when the tumours measured 30-40 mm(3) and 85-100 mm(3). All control animals and one of five (20%) mice treated with 3 mCi kg(-1) (213)Bi-plasminogen activator inhibitor type 2 developed metastases in the lymph nodes while no lymphatic spread of cancer was found in the 6 mCi kg(-1) treated groups at 2 days and 2 weeks post-cell inoculation. These results demonstrate that this novel (213)Bi-plasminogen activator inhibitor type 2 conjugate selectively targets prostate cancer in vitro and in vivo, and could be considered for further development for the therapy of prostate cancer, especially for the control of micro-metastases or in minimal residual disease.

In vitro cytotoxicity of bismuth-213 (213Bi)-labeled-plasminogen activator inhibitor type 2 (alpha-PAI-2) on human breast cancer cells.

Metastasis is the principal cause of death in breast cancer patients. New and improved treatments for eradicating micrometastases are needed. To this end, a novel alpha-emitting protein construct, 213Bi-labelled plasminogen activator inhibitor type-2 (PAI-2) (alpha-PAI-2), was evaluated in vitro. This construct exploits: (a) the overexpression of the cell-surface receptor bound urokinase plasminogen activator (uPA) in the metastatic spread of breast cancer cells; (b) the binding and inhibition of receptor-bound uPA by PAI-2; and (c) the high cytotoxicity of alpha radiation. High labeling efficiencies and stability of 213Bi bound to human recombinant PAI-2 conjugated with cyclic diethylenetriaminepentaacetic acid anhydride were achieved (greater than 90%). The uPA inhibitory activity of the chelated PAI-2 was maintained as determined by complex formation with uPA and by inhibition of uPA activity. Furthermore, the reactivity of alpha-PAI-2 was confirmed in a cell assay as this construct was highly cytotoxic to breast cancer cell lines that express active, receptor bound uPA. The specificity of alpha-PAI-2 targeting was shown using several controls. Firstly, an active uPA blocking agent that limits PAI-2 binding significantly improved cell survival by a factor greater than three. Secondly, a non-specific alpha-BSA construct had minimal cytotoxic effect. Moreover, alpha-PAI-2 was not cytotoxic to freshly isolated normal human leukocytes, confirming that cells which do not contain active, receptor bound uPA cannot be targeted by alpha-PAI-2. In conclusion, we have validated, in vitro, the potential of alpha-PAI-2 as a novel therapeutic agent for breast cancer.

In vitro and preclinical targeted alpha therapy of human prostate cancer with Bi-213 labeled J591 antibody against the prostate specific membrane antigen.

Limited options for the treatment of prostate cancer have spurred the search for new therapies. One innovative approach is the use of targeted alpha therapy (TAT) to inhibit cancer growth, using an alpha particle emitting radioisotope such as (213)Bi. Because of its short range and high linear energy transfer (LET), alpha-particles may be particularly effective in the treatment of cancer, especially in inhibiting the development of metastatic tumors from micro-metastases. Prostate-specific membrane antigen (PSMA) is expressed in prostate cancer cells and the neovasculature of a wide variety of malignant neoplasms including lung, colon, breast and others, but not in normal vascular endothelium. The expression is further increased in higher-grade cancers, metastatic disease and hormone-refractory prostate cancer (PCA). J591 is one of several monoclonal antibodies (mabs) to the extracellular domain of PSMA. Chelation of J591 mab with (213)Bi forms the alpha-radioimmunoconjugate (AIC). The objective of this preclinical study was to design an injectable AIC to treat human prostate tumors growing subcutaneously in mice. The anti-proliferative effects of AIC against prostate cancer were tested in vitro using the MTS assay and in vivo with the nude mice model. Apoptosis was documented using terminal deoxynucleotidyl transferase [TdT]-mediated deoxyuridinetriphosphate [dUTP] nick end-labeling (TUNEL) assay, while proliferative index was assessed using the Ki-67 marker. We show that a very high density of PSMA is expressed in an androgen-dependent human PCA cell line (LNCaP-LN3) and in tumor xenografts from nude mice. We also demonstrate that the AIC extensively inhibits the growth of LN3 cells in vitro in a concentration-dependent fashion, causing the cells to undergo apoptosis. Our in vivo studies showed that a local AIC injection of 50 microCi at 2 days post-cell inoculation gave complete inhibition of tumor growth, whereas results for a non-specific AIC were similar to those for untreated mice. Further, after 1 and 3 weeks post-tumor appearance, a single (100 microCi/100 microl) intra-lesional injection of AIC can inhibit the growth of LN3 tumor xenografts (volume<100 mm(3)) in nude mice. Tumors treated with AIC decreased in volume from a mean 46+/-14 mm(3) in the first week or 71+/-15 mm(3) in the third week to non-palpable, while in control mice treated with a non-specific AIC using the same dose, tumor volume increased from 42 to 590 mm(3). There were no observed side effects of the treatment. Because of its in vitro cytotoxicity and these anti-proliferative properties in vivo, the (213)Bi-J591 conjugate has considerable potential as a new therapeutic agent for the treatment of prostate cancer.

In vitro testing of the leukaemia monoclonal antibody WM-53 labeled with alpha and beta emitting radioisotopes.

We report the preparation and testing of a new alpha emitting radio-immunoconjugate (RIC) against acute myeloid leukaemia (AML) using CD33 positive monoclonal antibody WM-53 (specific for HL-60 cell line). Using cyclic anhydride of diethylenetriaminepentacetic acid (cDTPAa) as chelator, antibody was labeled with 213Bi (alpha), 149Tb (alpha), 153Sm (beta) and 152Tb (positron). In vitro testing showed high labeling efficiency (90-95%) and stability (11-19% leaching) with immunoreactivity virtually the same before and after labeling. DNA synthesis data and MTS cell survival were compared for all RICs. Only the alpha emitter was found to be capable of inhibiting DNA synthesis and had selective cell kill with activity as low as 2-3 microCi. The high stability and outstanding cytotoxicity of the 213Bi conjugate provides the basis for targeted alpha therapy for the control of metastatic and disseminated cancer such as AML.

Monte Carlo modeling of the effects of injected short-, medium- and longer-range alpha-particle emitters on human marrow at various ages.

The effects of injected short-, medium- and longer-range alpha-particle emitters ((149)Tb, (211)At/(211)Po and (213)Bi/(213)Po, respectively) on the total hemopoietic stem cell population of active normal bone marrow in humans of various ages has been estimated using Monte Carlo modeling. The fraction of the normal hemopoietic stem cells that are hit and survive has been calculated as a first step toward estimating the risk of development of therapy-induced leukemia. The fraction was lowest for the shorter-range alpha-particle emitter ((149)Tb) and highest for the longer-range alpha-particle emitter ((213)Bi/(213)Po), with the value for the medium-range alpha-particle emitter (211)At/(211)Po being intermediate between these. There was little variation in the data with the age of the subject within each alpha-particle emitter. This lack of age dependence provides reassurance that the fraction of cells hit in any subject of any age with normal marrow can be estimated by modeling newborn marrow (which requires little computing time) despite age-related differences in microarchitecture.

In vitro study of relationship between signal intensity and gadolinium-DTPA concentration at high magnetic field strength.

Although gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) has been used as a contrast material in MRI, it is known that the contrast enhancement effect is not uniform for high concentrations of Gd-DTPA. In order to evaluate the proper pulse sequences for dynamic MRI in aqueous solutions of Gd-DTPA, blood samples and melanoma cells, the signal intensity for several concentrations of Gd-DTPA were measured under inversion recovery (T1-weighted) at high magnetic field strength (7.0 Tesla). For aqueous solutions of Gd-DTPA, signal intensity correlated linearly with the concentration of Gd-DTPA between 0 mmol/L and 4 mmol/L. Using blood and melanoma cells, signal intensity correlated non-linearly with the concentration of Gd-DTPA between 0 mmol/L and 1.5 mmol/L. For concentrations of more than 4 mmol/L in aqueous solutions of Gd-DTPA, 1 mmol/L in blood and 1.5 mmol/L in melanoma, signal intensity decreased with increased Gd-DTPA concentration.

In vivo studies of Gd-DTPA-monoclonal antibody and gd-porphyrins: potential magnetic resonance imaging contrast agents for melanoma.

New tumor-specific contrast agents for clinical imaging and therapy for cancer are required. To this end Gd-H (Gd-hematoporphyrin), Gd-TCP (Gd-tetra-carboranylmethoxyphenyl-porphyrin), Gd-DTPA-WM53, and Gd-DTPA-9.2.27 were synthesized and administered by systemic injection to nude mice with human melanoma (MM-138) xenografts. The biodistribution T1 relaxation times and magnetic resonance (MR) image signal enhancement of the contrast agents are presented for the first time and compared for each group of five mice. A change (20%) in T1 relaxation times of water in human melanoma tumor xenografts was revealed 24 hours after injection of the labeled immunoconjugate Gd-DTPA-9.2.27. The percent of injected antibody or gadolinium that localized to the tumor was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) to be approximately 35%. A higher concentration of gadolinium was achieved compared with nonspecific compounds, indicating selective delivery of Gd-DTPA-9.2.27 to the melanoma xenografts. Porphyrin-based contrast agents (Gd-H and Gd-TCP) also showed significant uptake in melanomas. The uptake of Gd-TCP by the tumor was sufficient to deliver boron atoms into the tumor, making possible dual use for both MR imaging (MRI) and boron neutron capture therapy (BNCT). The linear relationship found between the paramagnetic contribution to the relaxation rates and contrast agent concentration allows quantitative studies of paramagnetic contrast agent uptake.