Schematic of various liposomal-Gd agents.

<p>Core-encapsulated gadolinium (CE-Gd) liposomes contain conventional low molecular-weight Gd-chelates in the core interior of the liposomes, surface-conjugate gadolinium (SC-Gd) liposomes contain Gd-chelates conjugated on the internal and external surface of the liposome bilayer, Dual-Gd liposomes contain both core-encapsulated and surface-conjugated Gd-chelates. The stars represent Gd-chelates.</p

<i>In vivo</i> comparison of liposomal-Gd contrast agents.

<p>Coronal maximum intensity projection (MIP) images of the head and thorax in mice acquired pre-contrast, post CE-Gd liposomes, post SC-Gd liposomes and post Dual-Gd liposomes. The contrast agents were administered intravenously at a lipid dose of 200 mg/kg. Please note the increased signal in the vessels compared to background and the high vessel conspicuity for smaller vessels (arrows in the Dual-Gd image). All images were acquired in different animals using the 3D-FSPGR sequence. The MIP images are presented at identical gray-scale levels.</p

T1 relaxivity of liposomal-Gd formulations on a per nanoparticle basis.

<p>T1 relaxivity of liposomal-Gd formulations on a per nanoparticle basis.</p

<i>In vivo</i> comparison of signal to noise ratios (SNR) (Fig. A) and contrast to noise ratios (CNR) (Fig. B) for different liposomal-Gd agents.

<p>Each agent was administered in mice at a lipid dose of 200 mg/kg. There was significant difference within the SNRs and CNRs of various contrast agents (p<0.05).</p

Characterization of liposomal-Gd formulations.

<p>Characterization of liposomal-Gd formulations.</p

T1 relaxation rates (R1) of liposomal-Gd formulations for different lipid doses.

<p>Measurements were performed at 1.5 Tesla MR field strength in bovine plasma at 37°C. For each lipid dose, the R1 values were significantly different for each of the liposomal-Gd agent (* corresponds to p<0.05).</p

Representative transverse <i>in vivo</i> CT images of rabbit hind leg VX2 tumors.

<p>(a) Unenhanced (without contrast) CT image acquired 24 days after VX2 inoculation in both thighs. Tumors appear as areas of low attenuation (arrows) and are relatively difficult to visualize. (b) Graph shows that weight derived from unenhanced CT images acquired 24 days after VX2 inoculation correlates well with weight derived from excised tumors (r = 0.80, p<0.001, n = 14). (c) Contrast enhanced CT image 24 days after VX2 inoculation in both thighs showing well-define peripheral rim enhancement of each tumor (solid white arrows). Areas of non-enhancing necrosis (central low attenuation material) are seen inside the tumor. (d) Graph shows that weight derived (with necrosis) from contrast-enhanced CT images acquired 24 days after VX2 inoculation correlates highly with weight derived from excised tumors (r = 0.99, p<0.001, n = 14).</p

Graphs showing the correlation of image-based <i>in vivo</i> analysis with <i>ex vivo</i> biodistribution of ¹¹¹In-octreotide in VX2 tumors after <i>in vivo</i><b> gene transfer.</b>

<p>(a and b) Uptake of radioligand administered 2 weeks after adenovirus normalized to CT-derived tumor weight calculated without and with necrosis. Percentage of injected dose per gram (%ID/g) of excised VX2 tumors correlated with that derived from planar and CT images after 2 weeks of adenoviral infection (a) without necrosis (r = 0.71, p<0.01, Coefficient of the x-variable = .72, n = 14) and (b) with necrosis (r = 0.77, p<0.01, Coefficient of the x-variable = 2.16, n = 14). (c) <i>In vivo</i> evaluation of the radiotracer uptake (%ID/g) in viable tumor (without necrosis) derived from planar and CT images after 3 days and 2 weeks of adenoviral infection, correlated with excised VX2 tumors (r = 0.80, p<0.001, Coefficient of the x-variable = 0.68, n = 32).</p

<i>In vivo</i> and <i>ex vivo</i>¹¹¹In-octreotide biodistribution.

<p>(a and b) <i>In vivo</i> radioligand biodistribution normalized to tumor weight (%ID/g) calculated with (a) and without (b) necrosis at 5 days and 2 weeks after infection with Ad-CMV-HA-SSTR2 or control Ad-CMV-GFP (*, p<0.05 compared with GFP). Normalizing for necrosis demonstrates that the apparent loss of expression at the later 2 week time point (compared with 5 days) post infection is less when the confounding variable of necrosis is removed. (c) Graph showing <i>ex vivo</i> tissue biodistribution of ¹¹¹In-octreotide in multiple organs in rabbits bearing VX2 tumors 2 weeks post virus infection. Significantly greater uptake was seen in tumors infected with Ad-CMV-HA-SSTR2 by IA or IT routes compared to tumors infected with control Ad-CMV-GFP (c and d: *, p<0.001 for IA, n = 6; p<0.01 for IT, n = 4) and this is confirmed by Western blotting. (d) Graph showing the %ID/g was significantly higher in viable tumor tissue infected with Ad-CMV-HA-SSTR2 compared to tumor necrosis (p<0.01 for IA, n = 6, p<0.02 for IT, n = 4) or muscle (p<0.001 for IA, n = 6, p<0.02 for IT, n = 4) in tumors infected by Ad-CMV-HA-SSTR2, but not control Ad-CMV-GFP.</p

<i>Ex vivo</i> analysis of ¹¹¹In-octreotide biodistribution in VX2 tumors 3 days after adenoviral infection.

<p>(a) Graph showing significantly higher biodistribution in tumors infected with Ad-CMV-HA-SSTR2 after IA and IT administration compared to tumors infected with control Ad-CMV-GFP (*, p<0.01 for IA, n = 6 and p<0.02 for IT, n = 6). The %ID/g was higher in viable tumor tissue compared to areas of tumor necrosis (p<0.001 for IA and p<0.01 for IT, n = 6) or muscle (p<.001 for IA and p<0.001 for IT, n = 6). (b) Graph showing <i>ex vivo</i> tissue biodistribution of ¹¹¹In-octreotide in multiple organs of rabbits bearing VX2 tumors infected <i>in vivo</i> with Ad-CMV-HA-SSTR2 or control virus. As in (a), increased uptake was seen in tumors infected with Ad-CMV-HA-SSTR2 by intra-arterial and intra-tumoral routes compared to tumors infected by intra-tumoral route with control Ad-CMV-GFP and this was further confirmed by Western blotting.</p