Tumor-induced lymph node alterations detected by MRI lymphography using gadolinium nanoparticles.
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.
Affiliation: Seattle Cancer Care Alliance, Seattle WA USA.
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.
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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.
No MeSH data available.