A shows a volume rendering of a mouse 30 minutes after i.v. injection of ExiTron nano 12000.

<p>B is a curved maximum intensity projection in coronal orientation of the same scan. A and B demonstrate the feasibility to perform CT angiography during the early intravascular phase of the tested contrast agent. Additionally, A and B show the early contrast agent uptake by the RES with increasing contrast of liver and spleen. C is a coronally oriented curved maximum intensity projection of a mouse that did not receive contrast agent.</p

Time course of contrast enhancement within the vascular system and the liver of C57BL/6J mice (n = 3 per group) after a single i.v. injection of 100 µl ExiTron nano 6000 or ExiTron nano 12000.

<p>Measurements were performed by placing a ROI within the left ventricle (vessel contrast) and within the liver avoiding large intrahepatic vessels. The baseline level ( = 100%) refers to measurement of the relative density of the liver and the vascular system prior to administration of contrast agent.</p

A and B show intrasplenic (*) and intrahepatic (LMet) growing tumors 26 days after intrasplenic injection of C15A3 colon tumor cells.

<p>A and B were acquired 4 hours after i.v. injection of 100 µl ExiTron nano 12000. B, C, and D illustrate contrast enhancement of the abdominal and mediastinal lymph nodes (LN) and of the adrenal glands (AdrG). C was acquired 4 hours after i.v. injection of 100 µl ExiTron nano 12000; D was acquired 22 days after i.v. injection of 100 µl ExiTron nano 12000. Micro-CT scanning parameters: 40 sec scan time; 190° rotation; 1200 projections; voxel size 41×41×55 µm³.</p

A and B show a partial diaphragmatic herniation of the left upper liver lobe in coronally (A) and sagittally (B) reconstructed maximum intensity projections of a C57BL/6J mouse 22 hours after i.v. injection of 100 µl ExiTron nano 12000.

<p>The herniated liver tissue can be easily delimited from the adjacent heart due to the positive liver contrast. C and D are micro-CT scans of the murine liver before (C) and 24 hours after (D) intravenous administration of 100 µl ExiTron nano 6000.</p

The development of liver metastases in mice monitored by micro-CT.

<p>To establish a suitable pre-screening routine, a separate group of animals was subjected to a time-series of micro-CT scans. Images were acquired 3 h post injection of a single dose of hepatocyte-specific contrast agent (ExiTron nano 6000) without the use of additional injections for follow-up. Images were collected at days 9 to 19 and days 20 to 49 for CEA-negative MC38 or CEA-positive C15A.3 metastases, respectively. Arrows indicate the same metastases at different time points for both cell lines. Note the differences in the size and number of metastases originating from MC38 (upper row) compared to C15A.3 (lower row).</p

Liver histopathology of metastases derived from CEA-positive C15A.3 murine tumor cells (A–C) or CEA-negative parental MC38 colon tumor cells (D–F).

<p>(A, D) H&E staining of liver metastases surrounded by normal tissue. (B, E) Higher magnification, emphasizing the difference in the tumor cell growth patterns with respect to the normal-to-tumor tissue border. (C, F) Immunohistochemistry of serial sections stained for CEA with CEA-specific M5A antibody confirming the CEA-expression status of the metastases. Note many central necrotic cells as indicated by arrows in B, C and E in both metastases. Bar size (A, D) 125 µm, all other 50 µm.</p

MRI and PET scan results for liver metastases originating from C15A.3 and MC38 cells 24 h post-injection of ⁶⁴Cu-DOTA-M5A antibody.

<p>MRI images clearly show the location of the liver metastases (arrows) and were used to draw regions of interest (ROIs) for evaluating the PET data. Immuno-PET images indicate strong signals in the areas of the CEA-positive C15A.3-derived liver metastases. No enhanced tracer uptake was observed in the areas of CEA-negative MC38 derived metastases.</p

Uptake of the ⁶⁴Cu-DOTA-labeled M5A antibody in CEA-positive C15A.3- and CEA-negative MC38-derived liver metastases.

<p>(A) Depicted are the %ID/cc of the labeled M5A antibody in either C15A.3 or MC38 derived metastases and the uptake of the control antibody hu14.18 at three different time points post injection of antibodies. For blocking experiments, 500 µg of unlabeled M5A was injected 3 h prior to labeled M5A. (B) The ratio of the antibody uptake between metastases and healthy liver. For A+B n = 8 animals for C15A.3+M5A, n = 7 animals for MC38+M5A, n = 2 animals for blocking and n = 4 animals for control antibody (hu14.18). All animals were scanned at every time-point. (C) %ID/cm³ of ⁶⁴Cu-DOTA-labeled M5A antibody in several organs at different time points. (D) Focus on the %ID/cm³ of ⁶⁴Cu-DOTA-labeled M5A in the right ventricle. For C+D n = 7 at all time points. Statistically significant results are designated with * when p≤0.05.</p

<i>Ex vivo</i> autoradiography (A), H&E staining (B, D) and M5A-immunohistochemistry (C, E) of the CEA-positive C15A.3-derived metastases.

<p>Evaluation of the cryosections was performed 24 h post-injection of ⁶⁴Cu-DOTA-M5A antibody. (A) Autoradiography shows the heterogeneous distribution of M5A within metastases. (B, C) The location of metastases in H&E and immunostaining correlates with the location of the metastases shown in (A). Note the intense, dark staining of the C15A.3 tumor cells near the tumor-to-normal border (D, E arrows). Bar size A-C 3 mm and C-D 200 µm respectively.</p

Additional file 1: of Integrating clinical decision support systems for pharmacogenomic testing into clinical routine - a scoping review of designs of user-system interactions in recent system development

PRISMA checklist for the process of searching and selecting articles. Information is provided for 22 out of 27 points recommended. (DOC 63 kb