Time-course characterization of the computed tomography contrast enhancement of an iodinated blood-pool contrast agent in mice using a volumetric flat-panel equipped computed tomography scanner

OBJECTIVE: The objective of this study was to determine the time-course of computed tomography (CT) contrast enhancement of an iodinated blood-pool contrast agent. METHODS: Five C57BL/6 mice were anesthetized, imaged at baseline, and given an iodinated blood-pool contrast agent. Micro-CT scans were acquired at 0, 0.25, 0.5, 1, 2, 4, 8, and 24 hours after injection. The mean CT number was determined in a region of interest in 7 organs. RESULTS: The CT contrast enhancement was plotted as a function of time for each organ. We identified an imaging window immediately after injection suitable for visualizing the vascular system and a second imaging window at 24 hours for visualizing liver and spleen. CONCLUSIONS: A single injection of the blood-pool contrast agent can be used for dual-phase investigations of the vasculature (t = 0 hours) and liver (t = 24 hours), which can be applied to studies of liver tumors or disease.     

Characterization of continuously extruded iopromide-carrying liposomes for computed tomography blood-pool imaging.

RATIONALE AND OBJECTIVES: Contrast-carrying liposomes are potentially useful as computed tomography (CT) blood-pool agents. In the present study, preliminary safety, pharmacokinetics, and the CT imaging behavior of continuously extruded iopromide-carrying liposomes were studied. METHODS: Iopromide liposomes were prepared by continuous high-pressure extrusion. Cell membrane-damaging characteristics were assessed in vitro in dog erythrocytes. Acute and subchronic toxicity and pharmacokinetics parameters were determined in rats. Computed tomography imaging efficiency was studied in rabbits. RESULTS: The iopromide-carrying liposomes caused only minor morphological changes in dog erythrocytes. The median lethal dose in rats was approximately 4.5 g of total iodine per kilogram of body weight. In a subchronic tolerance study in rats that were administered six doses of 1 g iodine per kilogram twice a week, no adverse effects were observed. The pharmacokinetics in rats was dose dependent, and elimination of iopromide was almost complete within 7 days after intravenous administration. In rabbits, at a dose of 300 mg total iodine per kilogram, the iopromide-carrying liposomes displayed prolonged blood circulation, with mean CT density differences > 60 Hounsfield units (aorta) for up to 10 minutes. CONCLUSIONS: The iopromide liposomes were well tolerated, almost completely excreted, and have potential as a CT blood-pool imaging agent.     

Preclinical profile of the monodisperse iodinated macromolecular blood pool agent P743

RATIONALE AND OBJECTIVES: To summarize the chemical synthesis, physicochemical characterization, pharmacokinetic behavior, and biological evaluation of P743, a new macromolecular iodinated contrast medium. METHODS: The synthesis and molecular modeling of the iodinated macromolecule P743 are described. The pharmacokinetic profile was established in rabbits and rats. Acute toxicity in mice, renal tolerance in normal rabbits, and renal tolerance in uninephrectomized, dehydrated rats undergoing selective intrarenal injection was evaluated. In vitro permeability effects on isolated mastocytes and on the coagulation pathways were carried out. Computed tomography vascular imaging was performed after intravenous injection of P743 (300 mg I/kg) in rabbits and compared with the nonspecific nonionic agent iobitridol. RESULTS: P743 is a monodisperse, macromolecular iodinated contrast medium. In both rabbits and rats, P743 showed a pharmacokinetic profile consistent with that of a rapid-clearance blood-pool agent. Its diffusion through the endothelium was found to be low in vitro, thus confirming early confinement of this macromolecule, unlike nonspecific contrast media. In both species, P743 was excreted by glomerular filtration. Acute toxicity disclosed no mortality at the highest volume that could be injected into mice, leading to a median lethal dose greater than 8.9 g I/kg. Renal tolerance was found to be good in both euvolemic rabbits and uninephrectomized, dehydrated rats. No histamine or leukotriene B4 release was found on RBL-2H3 isolated mastocytes. P743 did not interfere with the coagulation pathways. Imaging experiments confirmed that P743 remains in the vascular compartment for a longer time than does iobitridol, thus allowing vascular enhancement that is twice as high as that of iobitridol in the recirculation phase. CONCLUSIONS: The pharmacokinetic and imaging profiles of P743, a new, monodisperse, macromolecular blood-pool iodinated contrast medium, were consistent with those of a rapid-clearance blood-pool agent. Its initial safety profile is satisfactory. Further experimental imaging studies are required to define the clinical interest in such molecules.     

Potential dependent superiority of gold nanoparticles in comparison to iodinated contrast agents

Purpose

To identify the benefits in image contrast enhancement using gold nanoparticles (AuNPs) compared to conventional iodinated contrast media.

Materials and methods

Gold nanoparticles and iodinated contrast media were evaluated for contrast enhancement at various X-ray tube potentials in an imaging phantom. Iopromide and AuNP suspension were equalized according to molar concentration of radiopaque element (0.5077 Mol/L). Contrast-to-noise ratio is used to quantify contrast enhancement. Both projectional radiographic (40-80 kVp) and computed tomography (CT) (80-140kVp) imaging modalities were examined.

Results and conclusions

Findings indicate 89% improvement in CNR at low energies near the mammographic range (40 kVp). However, as expected no significant difference in enhancement was observed at potentials commonly used for angiography (around 80 kVp) probably due to the k-edge influence for iodine. At the highest energies typically available in computed tomography, significant improvement in contrast enhancement using gold nanoparticles is obtained, 114% greater CNR than that produced by iodine at 140 kVp. Experimental findings for 70-120 kVp spectra correlate well with the theoretical calculations based on linear attenuation coefficients. Superior attenuation of gold nanoparticles at low and high kVp potentials support their further (pre)clinical evaluation.     

Glucose-receptor MR imaging of tumors: study in mice with PEGylated paramagnetic niosomes

PURPOSE: To evaluate a magnetic resonance (MR) imaging contrast agent for tumor detection based on paramagnetic nonionic vesicles (niosomes) bearing polyethylene glycol (PEG) and glucose conjugates for the targeting of overexpressed glucose receptors. MATERIALS AND METHODS: Four gadobenate dimeglumine-loaded niosome preparations including nonconjugated niosomes, niosomes bearing glucose conjugates (N-palmitoyl glucosamine [NPG]), niosomes bearing PEG 4400, and niosomes bearing both PEG and NPG were tested. In vitro cellular uptake was measured at electron paramagnetic resonance (EPR) after incubation with human prostate carcinoma, PC3, cells. In vivo distribution was studied at MR imaging 6, 12, and 24 hours after injection, with assessment of tumor, brain, liver, and muscle signal intensity (SI) in 49 mice bearing PC3 cells. Efficiency of targeted contrast agents was assessed with tumor-to-muscle contrast-to-noise ratio (CNR). Testing for differences was performed with analysis of variance followed by a posteriori Fisher test. RESULTS: In vitro, gadolinium could be detected at EPR only in cell pellets incubated with niosomes bearing glucose conjugates or niosomes bearing both glucose conjugates and PEG (4.9. 10(-15) and 4.5. 10(-15) mol gadolinium per PC3 cell). In vivo, marked predominant tumor enhancement was demonstrated 24 hours after injection of glycosylated PEG niosomes (P <.01); no significant differences were observed following injection of nonconjugated niosomes, glycosylated niosomes, or PEG 4400 niosomes. Twenty-four hours after injection, sole presence of NPG or PEG 4400 on the surface of the niosome led to higher tumor-to-muscle CNR than that observed after injection of nonconjugated niosomes (CNR of 3.3 +/- 0.7 [SD], 3.4 +/- 2.2, and 0 +/- 1.9). Combination of NPG and PEG led to even higher tumor-to-muscle CNR (6.3 +/- 2.2). CONCLUSION: Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.     

In vivo imaging of T cells loaded with gold nanoparticles: a pilot study

Purpose

Malignant tumours develop strategies to avoid immune recognition and elimination by T cells, even in individuals with a fully functioning immune system. To explore the treatment approach of adoptive immunotherapy, we exploited T cells loaded with radiolabelled gold nanoparticles (AuNPs) to track T cells in vivo.

Materials and methods

Surface-modified AuNPs were radiolabelled with ¹¹¹In or ⁶⁴Cu. They were then transferred into T cells via electroporation. To evaluate the effectiveness of this process, T cells loaded with ¹¹¹In-radiolabelled AuNPs were injected directly into the right lung of nude mice for in vivo imaging by micro-SPECT/CT. T cells loaded with ⁶⁴Cu-radiolabelled AuNPs were then injected into the tail vein of nude mice and imaged by micro-PET/CT.

Results

High uptake signals were observed in the right lung following the direct injection of T cells containing ¹¹¹In-labelled AuNPs. Imaging showed a marked difference in the dynamic biodistribution of T cells containing ⁶⁴Cu-labelled AuNPs when compared with ⁶⁴Cu-labelled AuNPs alone.

Conclusions

This study demonstrated the feasibility of the in vivo imaging of T cells loaded with radiolabelled AuNPs.     

优维显偶联抗结肠癌单克隆抗体荷瘤裸鼠CT成像的实验研究

目的：建立优维显与单克隆抗体偶联的方法，阐明ＣＴ免疫成像的生物学基础。材料与方法：制备非离子型造影剂优维显与抗结肠癌单克隆抗体ＣＭＵ１５的偶联物，建立人结肠癌荷瘤裸鼠模型，向荷瘤裸鼠体内注射上述偶联物后，行动态ＣＴ扫描。结果：注射后早期肿瘤部位与非肿瘤部位的ＣＴ值差异不明显。６～４８小时，肿瘤部位出现明显的造影剂浓聚，显示出与周围组织的清晰对比，ＣＴ值明显增高，同时肿瘤周围的解剖结构也获得了清晰地显示。结论：将ＣＴ的影像技术优势与单克隆抗体的准确性、特异性和敏感性相结合，通过对肿瘤ＣＴ免疫成像各种征象的认识，可望成为肿瘤导向诊断研究的一项新的方法。     

Long-residence-time nano-scale liposomal iohexol for X-ray-based blood pool imaging

RATIONALE AND OBJECTIVES: Although soluble nonionic iodine compounds with low systemic toxic effects have been developed for use in computed tomography (CT), they have short residence times of a few minutes or mere seconds-insufficient time for blood pool imaging, even with high-speed multi-detector row spiral CT. Moreover, potential renal toxic effects preclude repeated administration of these contrast agents during imaging, as well as their use in patients with compromised renal function. The objective of this study was to develop and evaluate a CT contrast agent for blood pool imaging that remains in the blood for more than 3 hours and that is relatively nontoxic to the kidneys. MATERIALS AND METHODS: The authors assessed a liposomal iohexol formulation for its encapsulation efficiency in terms of milligrams of iodine per milliliter of lipid formulation and for its stability in phosphate buffer solution and in human plasma in vitro. Using a rabbit model, they also assessed the formulation's in vivo stability, residence time, and enhancement of contrast on images of various organ systems. RESULTS: The formulation, which contained 34.8 mg of iodine per milliliter of liposomal iohexol solution, remained stable in blood plasma both in vitro and in vivo, after injection into rabbit vasculature. An intravenous dose of 475 mg of iodine per kilogram of body weight produced contrast enhancement in the rabbit model of approximately 130 HU in the aorta and liver cortex and approximately 100 HU in the kidney cortex. Contrast enhancement was maintained for 3 hours after injection, and minimal clearance of the contrast agent via the kidneys was observed. CONCLUSION: The liposomal iohexol formulation tested in this study had a sufficient residence time for blood pool imaging in a rabbit model. Future experiments with long-residence-time iohexol formulations may lead eventually to applications in cardiac imaging and in early tumor detection.     

Initial computed tomography imaging experience using a new macromolecular iodinated contrast medium in experimental breast cancer

OBJECTIVE: The objective of this study was to evaluate computed tomography (CT) enhancement characteristics for a new iodinated macromolecular contrast medium (MMCM), PEG12000-Gen4-triiodo, for angiographic effect and for assessment of abnormal vascular permeability in cancer. MATERIALS AND METHODS: Time persistence of angiographic effect was evaluated on rat CT images acquired over 30 minutes using the iodinated polyethyleneglycol- (PEG) based macromolecule. Dynamic CT imaging after PEG12000-Gen4-triiodo-enhancement in tumor-bearing rats was used to quantitatively estimate plasma volume and microvascular transendothelial permeability for both tumor and normal soft tissue. Using identical doses of iodine, 300 mg iodine/kg, blood curves for this MMCM and iohexol were compared. RESULTS: Serial whole-body CT angiograms using PEG12000-Gen4-triiodo showed diagnostic vascular detail through 20 minutes, and the blood enhancement curve was higher and more persistent than with small-molecular iohexol. Permeability estimates were significantly (P<0.02; paired t test) higher in tumors (48.2+/-18.1 microL/min-1 100 mL) than in muscle (2.5+/-5.7 microL/min-1 100 mL). CONCLUSIONS: Use of PEG-based MMCM for experimental CT allowed for a persistent angiographic enhancement and for quantitative estimation of tumor microvascular characteristics.     

Assessment of morphological MRI for pulmonary changes in cystic fibrosis (CF) patients: comparison to thin-section CT and chest x-ray

OBJECTIVES: As pulmonary complications are life limiting in patients with cystic fibrosis (CF), repeated chest imaging [chest x-ray, computed tomography (CT)] is needed for follow up. With the continuously rising life expectancy of CF patients, magnetic resonance imaging (MRI) as a radiation-free imaging modality might become more and more attractive. The goal of this study was to prospectively assess the value of MRI for evaluation of morphologic pulmonary CF-changes in comparison to established imaging modalities. MATERIALS AND METHODS: Thirty-one CF patients (19 female, 12 male; mean age 16.7 years) with stable lung disease were examined by MRI: HASTE, coronal/transversal (TR/TE/alpha/TA: infinite/28 ms/180 degrees /18 s), multi-detector computed tomography (MDCT) (30 patients): 120 kV, dose modulated mAs, and chest x-ray (21 patients). Image evaluation: random order, 4 chest radiologists in consensus; chest x-ray: modified Chrispin-Norman score; CT and MRI: modified Helbich score. The maximal attainable score for chest x-ray was 34, for MRI and CT 25. Median scores, Pearson correlation coefficients, Bland-Altman plots, and concordance of MRI to CT on a lobar and segmental basis were calculated. RESULTS: The median MRI and MDCT scores were 13 (min 3, max 20) respectively 13.5 (min 0, max 20). The median chest x-ray score was 14 (min 5, max 32). Pearson correlation coefficients: MRI/CT = 0.80, P < 0.0001; MRI/chest x-ray = 0.63, P < 0.0018; chest x-ray/CT = 0.75, P < 0.0001. The median lobe related concordance was 80% for bronchiectasis, 77% for mucus plugging, 93%, for sacculation/abscesses, and 100% for collapse/consolidation. CONCLUSIONS: Morphologic MRI of the lung in CF patients demonstrates comparable results to MDCT and chest x-ray. Because radiation exposure is an issue in CF patients, MRI might have the ability to be used as an appropriate alternative method for pulmonary imaging.     

Gated blood-pool SPECT versus cardiac magnetic resonance imaging for the assessment of left ventricular volumes and ejection fraction

Background  

We evaluated the accuracy of planar radionuclide angiography and different count-based and space-based electrocardiogram (ECG)-gated blood-pool single-photon emission computed tomography (GBPS) algorithms for assessment of left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) compared with the gold standard of cardiac magnetic resonance imaging (cMRI). The goal is to assess the accuracy of a recently developed GBPS algorithm.     

Early metabolic changes following chemotherapy of human gliomas in vivo demonstrated by phosphorus magnetic resonance spectroscopy

The authors have used phosphorus magnetic resonance spectroscopy to monitor pH changes in malignant gliomas following treatment with intravenous and intra-arterial 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU). Image-guided, localized phosphorus spectra of human gliomas in situ were obtained using a 1.5-T whole body combined imaging and spectroscopy system. Initial intravenous BCNU treatment was followed by a transient decrease of tumor intracellular pH by 0.15 +/- 0.03 pH units (mean +/- SD). Superselective intra-arterial administration of the same drug was followed by an increase of tumor intracellular pH by 0.15 +/- 0.6 pH units (mean +/- SD). These changes occurred prior to any changes on x-ray, computed tomography (CT), or magnetic resonance imaging (MRI). In addition to enhancing our understanding of the metabolic effects of BCNU, such changes may correlate with drug efficacy or toxicity and may be useful in guiding therapy in the future.     

Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.     

Micro-CT imaging with a hepatocyte-selective contrast agent for detecting liver metastasis in living mice

RATIONALE AND OBJECTIVES: Micro-computed tomography (CT) is a important tool for longitudinal imaging of tumor development. The detection and monitoring of tumors in the liver in live animals using micro-CT is challenging. We evaluated the feasibility of high-resolution micro-CT enhanced with a hepatocyte-selective contrast agent for detecting liver metastases in a live murine model. MATERIALS AND METHODS: Hepatic metastases were induced in 10 BALB/C mice. Two mice each were randomly selected on days 3, 5, 7, 10, and 13 after CT26 colon adenocarcinoma cells were injected into the portal vein; micro-CT imaging was performed at 10 minutes and 4 hours after intravenous administration of a hepatocyte-selective contrast agent at a dose of 0.4 mL/mouse. The attenuation values of the normal liver and the tumors were obtained. The number of metastases was counted and their sizes were measured on the micro-CT images. Gross or histopathologic evaluation was performed for correlating the liver tumors with the micro-CT images. RESULTS: A total of 74 separate tumor sites larger than 300 mum in diameter were detected on pathologic examination of the mice that were sacrificed 7 days after cell injection. On micro-CT, 66 of 74 tumors were detected (83.8%). The smallest tumor detected on micro-CT was 300 mum. There were eight false-negative readings on micro-CT. The sizes of the individual liver metastases measured by micro-CT and on the excised specimen were highly correlated (P < .001). The correlation between the CT scan measurement and the actual measurement was r = 0.8354 (P < .0001). CONCLUSIONS: High-resolution micro-CT enhanced with a hepatocyte-selective contrast agent can be a promising tool for detecting liver metastases in a live murine model.     

Improved visualization of vessels and hepatic tumors by micro-computed tomography (CT) using iodinated liposomes

OBJECTIVE: The goal of this study was to determine whether iodinated liposomes are a suitable tracer for mice microvessel and liver imaging by preclinical computed tomography (CT). MATERIALS AND METHODS: Iodinated liposomes were evaluated for vessel and liver imaging. A first group of nude mice was imaged by micro-CT after i.v. injection of liposomes at 1 or 2 gI/kg body weight (b.w.) for intervals up to 24 hours. A second group of mice bearing liver micrometastases was imaged after injection of liposomes at 2 gI/kg b.w. for intervals up to 24 hours. RESULTS: Vascular enhancements of 120 +/- 8 and 322 +/- 20 Hounsfield unit (HU) were obtained after injection of liposomes at 1 or 2 gI/kg b.w., respectively. This enhancement decreased with a blood half-life of 135 +/- 10 and 86 +/- 9 minutes, respectively. Liver enhancement of 157 +/- 5 and 235 +/- 23 HU were obtained after injection of iodinated liposomes at 1 and 2 gI/kg b.w., respectively. Liver micrometastases (250 microm) were detectable after injection of iodinated liposomes at 2 gI/kg b.w. CONCLUSIONS: Iodinated liposomes are a suitable contrast agent for vessels and liver imaging by micro-CT allowing clear vascular enhancement and detection of small liver metastases.     

Positron emission tomography as a diagnostic tool. A reassessment based on literature review.

Currently used clinical diagnostic imaging modalities, such as magnetic resonance imaging (MRI) and x-ray computed tomography (CT) provide predominantly anatomic information. CT images reflect x-ray attenuation distribution in the body, whereas MRI signals depend primarily on proton density and tissue relaxivity. In contrast to these predominantly anatomic modalities, positron emission tomography (PET) reflects tissue physiology and metabolism. Although PET has been used predominantly as a research tool, the clinical use of this technique for the detection, noninvasive characterization, and treatment planning of selected disease processes has been extensively studied in oncology, cardiology, and neurology. The author examined currently available literature to reassess the potential role of PET as a diagnostic tool in the following specific clinical situations: (1) the differentiation of radiation necrosis from tumor recurrence; (2) the characterization of the physiologic significance of coronary stenosis and the evaluation of the myocardial viability; and (3) the localization of the epileptogenic foci.     

Nitrogen-filled liposomes as a vascular US contrast agent: preliminary evaluation.

Liposomes with a mean diameter of 1-2 microns were made to entrap nitrogen gas and tested as an ultrasound (US) contrast agent. The gas-filled liposomes, or Aerosomes (ImaRx Pharmaceutical, Tucson) were tested in vitro for size, stability, reflectivity, and acoustic characterization, and were tested in vivo for acute toxicity in mice and for cardiac imaging in rabbits after intravenous injection. Aerosomes have much greater reflectivity and higher attenuation than do standard liposomes and retain their acoustic properties after storage in aqueous media for several months. The interpolated median lethal dose of Aerosomes is approximately 2.5 mmol of lipid per kilogram, and the imaging dose is under 5 mumol of lipid per kilogram, yielding a potential therapeutic index of over 500 to 1. Postcontrast US images showed sustained enhancement of all four cardiac chambers as well as enhancement in the aorta, vena cava, and hepatic veins. Aerosomes hold promise as a contrast agent for cardiac and blood-pool imaging. Further work is in progress to characterize and develop this novel US contrast agent.     

Micro-CT enables microlocalisation and quantification of Her2-targeted gold nanoparticles within tumour regions

Objectives

Gold nanoparticles are of interest as potential in vivo diagnostic and therapeutic agents, as X-ray contrast agents, drug delivery vehicles and radiation enhancers. The aim of this study was to quantitatively determine their targeting and microlocalisation in mouse tumour models after intravenous injection by using micro-CT.

Methods

Gold nanoparticles (15 nm) were coated with polyethylene glycol and covalently coupled to anti-Her2 antibodies (Herceptin). In vitro, conjugates incubated with Her2+ (BT-474) and Her2– (MCF7) human breast cancer cells showed specific targeted binding with a Her2+ to Her2– gold ratio of 39.4±2.7:1. Nude mice, simultaneously bearing subcutaneous Her2+ and Her2– human breast tumours in opposite thighs were prepared. Gold nanoparticles alone, conjugated to Herceptin or to a non-specific antibody were compared. After intravenous injection of the gold nanoparticles, gold concentrations were determined by atomic absorption spectroscopy. Microlocalisation of gold was carried out by calibrated micro-CT, giving both the radiodensities and gold concentrations in tumour and non-tumour tissue.

Results

All gold nanoparticle constructs showed accumulation, predominantly at tumour peripheries. However, the Herceptin–gold nanoparticles showed the best specific uptake in their periphery (15.8±1.7% injected dose per gram), 1.6-fold higher than Her2– tumours and 22-fold higher than surrounding muscle. Imaging readily enabled detection of small, 1.5 mm-thick tumours.

Conclusion

In this pre-clinical study, antibody-targeted 15 nm gold nanoparticles showed preferential uptake in cognate tumours, but even untargeted gold nanoparticles enhanced the visibility of tumour peripheries and enabled detection of millimetre-sized tumours. Micro-CT enabled quantification within various regions of a tumour.Antibodies bound to conventional iodine CT contrast agents have not provided sufficient targeted CT contrast since they only load around three iodine atoms per antibody. However, gold nanoparticles (AuNPs) can load antibodies with a greater number of heavier atoms. A 15 nm AuNP contains approximately 100 000 gold atoms, thus promising to provide useful X-ray contrast for targeted tumours [1,2]. AuNPs have been shown to confer designable blood half-lives from several minutes [3] to 15 h [2], making them interesting X-ray vascular imaging agents. Their blood half-lives are longer than iodine agents and promote better tumour uptake. Optical in vivo imaging has been achieved using near-infrared optical coherence tomography [4] or surface-enhanced Raman spectroscopy [5]. If tumours are targeted with AuNPs, they can be used for drug delivery [6], near-infrared hyperthermia ablation [4,7] or enhancement of radiotherapy [8-11]. However, the microlocalisation of AuNPs in tumours after intravenous (iv) injection has not been extensively studied. In this report, we quantify tumour loading by Herceptin-targeted and untargeted AuNPs in mice using micro-CT and atomic absorption spectroscopy. Trastuzumab (Herceptin) is a humanised monoclonal antibody currently used to treat human breast cancers with upregulated Her2 (human epidermal growth factor receptor 2) expression, which occurs in approximately 30% of breast cancer patients [12]. Tumour contrasting could be useful for early detection and visualising a tumour’s true extent to assist in image-guided surgeries, radiotherapy planning, non-invasive tumour typing, detection of lymph node involvement, drug, infrared and X-ray therapies, and monitoring.     

Volumetric imaging with ultrasonic spiral CT.

To examine the feasibility of implementing spiral computed tomography (CT) in ultrasonic imaging as a potential method for breast screening, an algorithm for x-ray spiral CT was applied to ultrasonic waves on a specially built ultrasonic tomographic system. Three-dimensional reconstructions of various phantoms were obtained. Spiral ultrasonic CT is feasible, and it may have clinical merit as a breast imaging method.