Non-invasive imaging of combretastatin activity in two tumor models: Association with invasive estimates

Figures & data

Figure 1. Necrotic fraction versus logarithmic tumor size for control animals (○) and animals treated with 100 mg/kg i.p. CA4P (●). Measurements were performed 24 hours following treatment. Left: C3H mammary carcinoma, right: KHT sarcoma. Results show mean (± 1 SE) for 6–18 mice/group.

Figure 2. Upper panel: Necrotic fraction measured 24 hours following no treatment (○), treatment with 10 mg/kg i.v. NLA alone (Δ), 100 mg/kg i.p. CA4P alone (□), or treatment with both NLA and CA4P (●). For the combined treatment, measurements were performed 24 hours following CA4P administration, and the abscissa shows the time point of NLA administration relative to the administration of CA4P, which was given at time point 0. Lower panel: Interstitial fluid pressure versus tumor size for control animals (○) and animals treated with 100 mg/kg i.p. CA4P 3 hours prior to the measurement (●). Left panels: C3H mammary carcinoma, right panels: KHT sarcoma. Results show mean (± 1 SE) for 6–18 mice/group.

Table I. DCE-MRI results.

	Initial DCE-MRI values (mean± 1 SE)
	C3H 200 mm^3 (n=7)	C3H 800 mm^3 (n=6)	KHT 200 mm^3 (n=8)	KHT 800 mm^3 (n=8)
IAUC [10^−3Ms]	15.3 ± 1.03	11.6 ± 2.05	11.7 ± 1.69	11.5 ± 1.18
K^trans [10^−3s^−1]	0.389 ± 0.0405	0.418 ± 0.0893	0.637 ± 0.0891	0.678 ± 0.0702
kep [10^−3s^−1]	4.15 ± 0.311	2.95 ± 0.317	5.57 ± 0.744	5.12 ± 0.354
ve [%]	8.84 ± 0.976	11.9 ± 1.12	13.2 ± 3.89	11.4 ± 0.977
vp [%]	4.58 ± 0.386	3.70 ± 0.697	3.14 ± 0.503	2.5 ± 0.328
	Relative change in DCE-MRI values in % (mean±1 SE)
	C3H 200 mm^3	C3H 800 mm^3	KHT 200 mm^3	KHT 800 mm^3
IAUC	−42.3 ± 8.99	−48.5 ± 5.45	−41.8 ± 10.4	−45.2 ± 10.3
K^trans	−26.8 ± 9.31	−55.0 ± 10.0	−43.3 ± 12.4	−61.2 ± 6.83
kep	−30.8 ± 7.54	−31.4 ± 7.75	−57.1 ± 9.13	−52.4 ± 9.44
ve	23.3 ± 9.30	−8.48 ± 5.19	32.8 ± 12.9	23.0 ± 11.0
vp	−58.1 ± 11.9	−59.1 ± 13.2	−58.9 ± 13.1	−57.2 ± 18.0

Figure 3. Example of images (inversion recovery with T_I = 2400 ms) and parameter maps produced by kinetic analysis: IAUC, K^trans, k_ep, v_e, and v_p. The images are produced for the same 200 mm³ KHT sarcoma before (left) and 3 hours after treatment with CA4DP (right). On the inversion recovery images, the light blue color shows the leg visible to the left of the tumor and the foot below the tumor, and the yellow line indicates 1 cm. The images and maps show intratumor heterogeneity and overall reduction of the vascular parameters IAUC, K^trans, k_ep, and v_p.