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Tumor-induced lymph node alterations detected by MRI lymphography using gadolinium nanoparticles.

Partridge SC, Kurland BF, Liu CL, Ho RJ, Ruddell A - Sci Rep (2015)

Bottom Line: The performance of three gadolinium contrast agents with different sizes and properties was compared by 3T MRI after subcutaneous injection.Gadolinium lipid nanoparticles were able to identify tumor-induced alterations in contrast agent drainage into the popliteal LN, while lower molecular weight or albumin-binding gadolinium agents were less effective.Surprisingly, second-tier tumor-draining inguinal LNs exhibited reduced uptake, indicating that tumors can also divert LN drainage.

View Article: PubMed Central - PubMed

Affiliation: Seattle Cancer Care Alliance, Seattle WA USA.

ABSTRACT
Contrast-enhanced MRI lymphography shows potential to identify alterations in lymph drainage through lymph nodes (LNs) in cancer and other diseases. MRI studies have typically used low molecular weight gadolinium contrast agents, however larger gadolinium-loaded nanoparticles possess characteristics that could improve the specificity and sensitivity of lymphography. The performance of three gadolinium contrast agents with different sizes and properties was compared by 3T MRI after subcutaneous injection. Mice bearing B16-F10 melanoma footpad tumors were imaged to assess tumor-induced alterations in lymph drainage through tumor-draining popliteal and inguinal LNs versus contralateral uninvolved drainage. Gadolinium lipid nanoparticles were able to identify tumor-induced alterations in contrast agent drainage into the popliteal LN, while lower molecular weight or albumin-binding gadolinium agents were less effective. All of the contrast agents distributed in foci around the cortex and medulla of tumor-draining popliteal LNs, while they were restricted to the cortex of non-draining LNs. Surprisingly, second-tier tumor-draining inguinal LNs exhibited reduced uptake, indicating that tumors can also divert LN drainage. These characteristics of tumor-induced lymph drainage could be useful for diagnosis of LN pathology in cancer and other diseases. The preferential uptake of nanoparticle contrasts into tumor-draining LNs could also allow selective targeting of therapies to tumor-draining LNs.

No MeSH data available.


Related in: MedlinePlus

Gd-LNP contrast media detects increased lymph drainage through the tumor-draining popliteal lymph node.(a) Full field-of-view oblique MIP image, illustrating the in vivo locations of the left and right popliteal (LPN and RPN, respectively) and inguinal LNs (LIN and RIN) that were analyzed in the study. The MIP was generated from 5 min post- GD-LNP images, in the same animal shown in part c. (b) Representative single slice images of LPN and RPN (arrows) from pre-contrast (0 min) and from 5 and 15 minute post-contrast scans after Gd-DTPA injection demonstrate modest LN enhancement after contrast injection. The orientation of the cortex and medulla is indicated. Arrowhead indicates the dark artifacts arising after contrast agent injection. (c) Single slice images of popliteal LNs after Gd-LNP injection show higher uptake into the LPN at 5 and 15 min. (d) Single slice images of popliteal LNs after Gd-FVT injection show uptake into the LPN and RPN at 5 min after contrast agent injection. Scale bars are indicated.
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f1: Gd-LNP contrast media detects increased lymph drainage through the tumor-draining popliteal lymph node.(a) Full field-of-view oblique MIP image, illustrating the in vivo locations of the left and right popliteal (LPN and RPN, respectively) and inguinal LNs (LIN and RIN) that were analyzed in the study. The MIP was generated from 5 min post- GD-LNP images, in the same animal shown in part c. (b) Representative single slice images of LPN and RPN (arrows) from pre-contrast (0 min) and from 5 and 15 minute post-contrast scans after Gd-DTPA injection demonstrate modest LN enhancement after contrast injection. The orientation of the cortex and medulla is indicated. Arrowhead indicates the dark artifacts arising after contrast agent injection. (c) Single slice images of popliteal LNs after Gd-LNP injection show higher uptake into the LPN at 5 and 15 min. (d) Single slice images of popliteal LNs after Gd-FVT injection show uptake into the LPN and RPN at 5 min after contrast agent injection. Scale bars are indicated.

Mentions: The 3T MRI lymphography performance of Gd-DTPA was compared with that of Gd-LNP and Gd-FVT in mice bearing B16-F10 tumors in the left rear footpad. Contrast agents injected into the feet drain to the left and right popliteal LNs (LPN, RPN), and then to the left and right inguinal LNs (LIN, RIN, Fig. 1a). Hypertrophy of the tumor-draining left popliteal LN (LPN) relative to the uninvolved right popliteal LN (RPN) could be appreciated in pre-contrast images, however subcutaneous injection of Gd-DTPA slightly improved delineation of the LPN margins (Fig. 1b). Gd-DTPA uptake into the LN margins was detectable at 5 min and at 15 min after injection. Gd-LNP nanoparticles (71–75 nm diameter) were readily taken up into the tumor-draining LPN, strongly enhancing the LN margins at 5 and at 15 min after injection, while the RPN showed less enhancement (Fig. 1c). We previously reported uptake of the intermediate size Gd-FVT contrast agent into the popliteal LNs using the same B16-F10 foot tumor model and 3T scanner protocols33. A representative example shows intermediate uptake of contrast into the LPN margins, and also into the RPN (Fig. 1d). The tumor-draining LPN as consistently enlarged in all 18 of the mice studied (median volume 2.6 mm3, range 1.2 to 5.0 mm3), was 3.3 times larger on average than the RPN (median 0.8 mm3, range (0.4 to 1.4 mm3; p < 0.001 by Wilcoxon signed rank test), in agreement with our previous studies12.


Tumor-induced lymph node alterations detected by MRI lymphography using gadolinium nanoparticles.

Partridge SC, Kurland BF, Liu CL, Ho RJ, Ruddell A - Sci Rep (2015)

Gd-LNP contrast media detects increased lymph drainage through the tumor-draining popliteal lymph node.(a) Full field-of-view oblique MIP image, illustrating the in vivo locations of the left and right popliteal (LPN and RPN, respectively) and inguinal LNs (LIN and RIN) that were analyzed in the study. The MIP was generated from 5 min post- GD-LNP images, in the same animal shown in part c. (b) Representative single slice images of LPN and RPN (arrows) from pre-contrast (0 min) and from 5 and 15 minute post-contrast scans after Gd-DTPA injection demonstrate modest LN enhancement after contrast injection. The orientation of the cortex and medulla is indicated. Arrowhead indicates the dark artifacts arising after contrast agent injection. (c) Single slice images of popliteal LNs after Gd-LNP injection show higher uptake into the LPN at 5 and 15 min. (d) Single slice images of popliteal LNs after Gd-FVT injection show uptake into the LPN and RPN at 5 min after contrast agent injection. Scale bars are indicated.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4620490&req=5

f1: Gd-LNP contrast media detects increased lymph drainage through the tumor-draining popliteal lymph node.(a) Full field-of-view oblique MIP image, illustrating the in vivo locations of the left and right popliteal (LPN and RPN, respectively) and inguinal LNs (LIN and RIN) that were analyzed in the study. The MIP was generated from 5 min post- GD-LNP images, in the same animal shown in part c. (b) Representative single slice images of LPN and RPN (arrows) from pre-contrast (0 min) and from 5 and 15 minute post-contrast scans after Gd-DTPA injection demonstrate modest LN enhancement after contrast injection. The orientation of the cortex and medulla is indicated. Arrowhead indicates the dark artifacts arising after contrast agent injection. (c) Single slice images of popliteal LNs after Gd-LNP injection show higher uptake into the LPN at 5 and 15 min. (d) Single slice images of popliteal LNs after Gd-FVT injection show uptake into the LPN and RPN at 5 min after contrast agent injection. Scale bars are indicated.
Mentions: The 3T MRI lymphography performance of Gd-DTPA was compared with that of Gd-LNP and Gd-FVT in mice bearing B16-F10 tumors in the left rear footpad. Contrast agents injected into the feet drain to the left and right popliteal LNs (LPN, RPN), and then to the left and right inguinal LNs (LIN, RIN, Fig. 1a). Hypertrophy of the tumor-draining left popliteal LN (LPN) relative to the uninvolved right popliteal LN (RPN) could be appreciated in pre-contrast images, however subcutaneous injection of Gd-DTPA slightly improved delineation of the LPN margins (Fig. 1b). Gd-DTPA uptake into the LN margins was detectable at 5 min and at 15 min after injection. Gd-LNP nanoparticles (71–75 nm diameter) were readily taken up into the tumor-draining LPN, strongly enhancing the LN margins at 5 and at 15 min after injection, while the RPN showed less enhancement (Fig. 1c). We previously reported uptake of the intermediate size Gd-FVT contrast agent into the popliteal LNs using the same B16-F10 foot tumor model and 3T scanner protocols33. A representative example shows intermediate uptake of contrast into the LPN margins, and also into the RPN (Fig. 1d). The tumor-draining LPN as consistently enlarged in all 18 of the mice studied (median volume 2.6 mm3, range 1.2 to 5.0 mm3), was 3.3 times larger on average than the RPN (median 0.8 mm3, range (0.4 to 1.4 mm3; p < 0.001 by Wilcoxon signed rank test), in agreement with our previous studies12.

Bottom Line: The performance of three gadolinium contrast agents with different sizes and properties was compared by 3T MRI after subcutaneous injection.Gadolinium lipid nanoparticles were able to identify tumor-induced alterations in contrast agent drainage into the popliteal LN, while lower molecular weight or albumin-binding gadolinium agents were less effective.Surprisingly, second-tier tumor-draining inguinal LNs exhibited reduced uptake, indicating that tumors can also divert LN drainage.

View Article: PubMed Central - PubMed

Affiliation: Seattle Cancer Care Alliance, Seattle WA USA.

ABSTRACT
Contrast-enhanced MRI lymphography shows potential to identify alterations in lymph drainage through lymph nodes (LNs) in cancer and other diseases. MRI studies have typically used low molecular weight gadolinium contrast agents, however larger gadolinium-loaded nanoparticles possess characteristics that could improve the specificity and sensitivity of lymphography. The performance of three gadolinium contrast agents with different sizes and properties was compared by 3T MRI after subcutaneous injection. Mice bearing B16-F10 melanoma footpad tumors were imaged to assess tumor-induced alterations in lymph drainage through tumor-draining popliteal and inguinal LNs versus contralateral uninvolved drainage. Gadolinium lipid nanoparticles were able to identify tumor-induced alterations in contrast agent drainage into the popliteal LN, while lower molecular weight or albumin-binding gadolinium agents were less effective. All of the contrast agents distributed in foci around the cortex and medulla of tumor-draining popliteal LNs, while they were restricted to the cortex of non-draining LNs. Surprisingly, second-tier tumor-draining inguinal LNs exhibited reduced uptake, indicating that tumors can also divert LN drainage. These characteristics of tumor-induced lymph drainage could be useful for diagnosis of LN pathology in cancer and other diseases. The preferential uptake of nanoparticle contrasts into tumor-draining LNs could also allow selective targeting of therapies to tumor-draining LNs.

No MeSH data available.


Related in: MedlinePlus