Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla

Abstract

Purpose: The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases.

Materials and Methods: 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE = 45/2.5 ms, alpha = 45°, TA = 1: 23 min, FOV = 5.12 × 5.12 cm², matrix = 256 × 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i. v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements.

Results: Mean SNRliver (Gd-DOTA: 14.6 +/–0.7; AGuIX: 28.2 +/–2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 +/–1.2; AGuIX: 29.6 +/–2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 +/–0.7; AGuIX: 15.4 +/–0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 +/–0.3; AGuIX: 14.0 +/–0.7, p < 0.001), mean CNR (Gd-DOTA: –2.5 +/–0.2; AGuIX: –7.5 +/–1.0, p < 0.001) and LE (Gd-DOTA: 3.8 +/–0.7; AGuIX: 14.9 +/–2.8, p = 0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout.

Conclusion: AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors.

Key Points:

• AGuIX provides superior enhancement as compared to the extracellular compound Gd-DOTA at 9.4 T.

• AGuIX may improve the detection and diagnostic sensitivity of malignant focal liver lesions.

• The small size of AGuIX allows for fast renal clearance and prevents undesirable accumulation in the body.

Citation Format:

• Fries P, Morr D, Müller A et al. Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla. Fortschr Röntgenstr 2015; 187: 1108 – 1115

Zusammenfassung

Ziel: Vergleich eines Gd-basierten Nanopartikels (AGuIX) mit einem extrazellulären, niedermolekularen Kontrastmittel (Gd-DOTA) zur MRT der Leber bei 9,4 T in Ratten mit hepatischen Metastasen eines kolorektalen Karzinoms.

Material und Methoden: 12 Ratten mit hepatischen Metastasen wurden mittels eines 9,4 T Tierscanners untersucht. Es wurden T1-gewichtete FLASH-Sequenzen (TR/TE = 45/2,5 ms, Flipwinkel = 45°, TA = 1: 23 min, FOV = 5,12 × 5,12 cm2, Matrix = 256 × 256) vor und an 10 Zeitpunkten nach KM-Gabe mittels Selbstgating akquiriert. Jedes Versuchstier erhielt 0,1 mmol/kg KG Gd-DOTA i. v. Zwei Tage später wurden die Untersuchungen nach Gabe von 0,01 mmol/kg KG AGuIX (entsprechend identischen Dosierungen an Gd) wiederholt. SNR von normalem Lebergewebe (SNRliver), stark und gering KM-affinen Anteilen der Tumoren (SNRtumor, hyperenh/SNRtumor, hypoenhanc), des Musculus erector spinae (SNRmuscle), CNR und Läsionsenhancement (LE) wurden basierend auf ROI-Messungen berechnet.

Ergebnisse: Die Mittelwerte des SNRliver (Gd-DOTA: 14,6 +/–0,7; AGuIX: 28,2 +/–2,6; p < 0,001), SNRtumor, hyperenhanc (Gd-DOTA: 18,6 +/–1,2; AGuIX: 29,6 +/–2,8, p < 0,001), SNRtumor, hypoenhanc (Gd-DOTA: 12,0 +/–0,7; AGuIX: 15,4 +/–0,7, p < 0,001), SNRmuscle (Gd-DOTA: 12,3 +/–0,3; AGuIX: 14,0 +/–0,7, p < 0,001), des CNR (Gd-DOTA: –2,5 +/–0,2; AGuIX: –7,5 +/–1,0, p < 0,001) und des LE (Gd-DOTA: 3,8 +/–0,7; AGuIX: 14,9 +/–2,8/p = 0,001) waren nach Gabe von AGuIX signifikant höher. Trotz der höheren Molekülmasse zeigt AGuIX analog zum niedermolekularen Komplex Gd-DOTA eine maximale Signalanreicherung unmittelbar nach Injektion gefolgt von einem kontinuierlichen Auswaschen.

Schlussfolgerungen: AGuIX zeigt ein besseres Enhancement als Gd-DOTA bei identischer Gd-Dosierungen. Dies basiert auf der Molekülstruktur und der konsekutiv verbesserten Interaktion mit Protonen, was zu einer Erhöhung der Relaxivität führt. AGuIX kann potenziell die Erkennbarkeit fokaler Leberläsionen und damit die Sensitivität bei der Diagnostik maligner Lebertumoren verbessern.

Kernaussagen:

• AGuIX zeigt bei 9,4 T bessere Kontrasteigenschaften im Vergleich zu dem extrazellulären Kontrastmittel Gd-DOTA.

• AGuIX kann dazu beitragen die Detektion fokaler Leberläsionen und damit auch die Sensitivität der MRT bei malignen Raumforderungen der Leber zu verbessern.

• Aufgrund der geringen Molekülgröße wird AGuIX schnell renal ausgeschieden und zeigt keine unerwünschte Akkumulation im Körper.

Key words

MR imaging - abdomen - metastases - contrast agents - gadolinium - experimental study

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