(A–D) MRI scans and graphs show osteolytic and
nonosteolytic bone tumors with gadolinium(III)-mono-5-hydroxytryptamide
of
2,2′,2′′-(10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic
acid) (Gd-5HT-DOTAGA). (A) Comparative morphologic
structure of representative osteolytic and nonosteolytic bone firefly
luciferase+MDA-MB-231 tumors shown as T2-weighted (T2w) spin-echo (SE)
maximum intensity pixel (MIP) projection images and T1-weighted
spin-echo pulse sequence 3.0-T MRI scans acquired in-section
pre-Gd-5HT-DOTAGA (pre-contrast) and after Gd-5HT-DOTAGA (post-contrast)
(0.15 mmol/kg) administration. The animals were preinjected with a
mixture of anti-epidermal growth factor receptor
(EGFR)-F(ab’)2-horseradish peroxidase (HRP) and
anti-EGFR-F(ab’)2-glucose oxidase (GOx) conjugates
before Gd-5HT-DOTAGA injection. (B) Dynamic contrast
enhancement in tumors (at 3.0-T MRI) expressed as contrast-to-noise
(CNR) ratio. CNR of bone tumor images in animals preinjected with
anti-EGFR conjugates before (pre) and 12 and 60 minutes after injection
of Gd-5HT-DOTAGA. CNR in animals with CT-confirmed osteolysis and
nonosteolytic tumors are shown compared with normal bone marrow (BM)
enhancement. Mean data are ± standard deviation (four tumors per
group, two to three MRI sections per animal). (C) CNR of
tumors in experimental and control groups (three tumors per group, two
to three MRI sections per animal); MRI was performed at 7.0 T. Control
group animals were preinjected with a blocking dose of cetuximab (5
mg/kg) before injection of a mixture of
anti-EGFR-F(ab’)2-HRP and
anti-EGFR-F(ab’)2-GOx conjugates. Significant
differences were observed at 12 minutes (first T1-weighted spin-echo
pulse sequence acquisition) and at 60 minutes after injection of
Gd-5HT-DOTAGA (0.2 mmol/kg). (D) Representative 7.0-T MRI
scans of invasive tumor: (1) T2-weighted spin-echo
maximum intensity pixel projection, (2)
pre-Gd-5HT-DOTAGA injection T1-weighted spin echo, (3)
12 minutes after Gd-5HT-DOTAGA injection T1-weighted spin echo,
(4) 60 minutes after Gd-5HT-DOTAGA injection
T1-weighted spin echo. Arrowheads point to the tumor in panels A and
D.