Feasibility of experimental BT4C glioma models for somatostatin receptor 2-targeted therapies

Figures & data

Figure 1. Visualization of BT4C tumors was suboptimal with [⁶⁸Ga]DOTATOC and [¹⁸F]FDR-NOC PET/CT. Representative (A) axial PET/CT image of a BDIX rat brain with an orthotopic BT4C glioma and (B) coronal PET/CT image of a mouse bearing a subcutaneous BT4C tumor in the neck after [⁶⁸Ga]DOTATOC injection i.v. (C,D) Representative coronal PET/CT images of the same mouse bearing a subcutaneous tumor in the left limb after [¹⁸F]FDR-NOC (C) and [¹⁸F]FDG (D) injections i.v. The tumor is clearly visualized with [¹⁸F]FDG PET/CT. Tumors are indicated with an arrow. PET images represent mean radioactivity concentration at 30–60 min after tracer injection. (E) Time-activity curves of BT4C tumors after injection with [⁶⁸Ga]DOTATOC or [¹⁸F]FDR-NOC. Uptake values are presented as mean SUV_max.

Table I. Tissue radioactivity measurements at 60 minutes after injection with [⁶⁸Ga]DOTATOC and [¹⁸F]FDR-NOC.

	Rat orthotopic BT4C glioma [^68Ga]DOTATOC n = 9	Mice subcutaneous BT4C tumor
		[^68Ga]DOTATOC n = 8	[^18F]FDR-NOC n = 8	p
Tumor	NA	0.31 ± 0.11	0.38 ± 0.04	*
Muscle	0.10 ± 0.04	0.05 ± 0.02	0.08 ± 0.01	*
Brain	NA	0.02 ± 0.02	0.03 ± 0.00	*
Heart	0.24 ± 0.06	0.10 ± 0.04	0.27 ± 0.04	**
Lung	0.70 ± 0.14	0.34 ± 0.09	0.81 ± 0.07	**
Liver	0.47 ± 0.40	0.12 ± 0.03	4.54 ± 0.34	**
Pancreas	NA	0.63 ± 0.23	0.68 ± 0.23
Spleen	0.56 ± 0.57	0.10 ± 0.03	0.25 ± 0.04	**
Small intestine	0.60 ± 0.20	0.18 ± 0.05	1.42 ± 0.69	**
Kidney	9.21 ± 4.87	2.73 ± 1.16	2.68 ± 0.29
Skin	0.33 ± 0.09	0.31 ± 0.11	0.41 ± 0.05	*
Blood	0.65 ± 0.16	0.28 ± 0.12	0.71 ± 0.10	**
Plasma	1.12 ± 0.25	0.25 ± 0.10	0.66 ± 0.11	**
Urine	113 ± 55.3	41.0 ± 15.8	26.5 ± 12.3
Tumor-to-muscle ratio	NA	6.46 ± 0.77	4.79 ± 0.64	*
Tumor-to-brain ratio	NA	22.3 ± 9.08	15.1 ± 1.91	*

Results are expressed as SUVs (mean± SD). NA = not analyzed. *p < 0.05; **p ≤ 0.001 between [⁶⁸Ga]DOTATOC and [¹⁸F]FDR-NOC in nude mice bearing subcutaneous BT4C tumors.

Figure 2. [¹⁸F]FDR-NOC is rapidly excreted via hepatobiliary and urinary pathways. Representative whole-body coronal PET images of mice i.v. injected with (A) [⁶⁸Ga]DOTATOC or (C) [¹⁸F]FDR-NOC and (B, D) corresponding time-activity curves for brain, heart, liver and kidney. Increased liver uptake of [¹⁸F]FDR-NOC can be clearly seen. Uptake values are presented as SUV_mean (± SD) of all mice. Dynamic PET images are averaged from 0 to 60 min after injection.

Figure 3. Autoradiography demonstrates high tumor uptake of [⁶⁸Ga]DOTATOC and [¹⁸F]FDR-NOC. Representative autoradiographs showing (A) uptake of [⁶⁸Ga]DOTATOC in rat orthotopic BT4C glioma, (C) uptake of [⁶⁸Ga]DOTATOC in subcutaneous BT4C tumor, and (E) uptake of [¹⁸F]FDR-NOC in another subcutaneous BT4C tumor. (B, D, F) Lower panel shows H&E stainings of the corresponding sections. Arrow indicates the tumor in rat brain. Bar = 1 mm.

Table II. Autoradiography results of tissue uptake of [⁶⁸Ga]DOTATOC and [¹⁸F]FDR-NOC.

	Rat orthotopic BT4C glioma [^68Ga]DOTATOC n = 7	Mice subcutaneous BT4C tumor
		[^68Ga]DOTATOC n = 8	[^18F]FDR-NOC n = 8	P
Tumor	9.8 ± 1.8	17.4 ± 7.5	75 ± 18	**
Muscle	1.2 ± 0.4	2.7 ± 1.6	18 ± 3.1	**
Brain	0.2 ± 0.1	ND	3.3 ± 1.2
Tumor-to-muscle ratio	9.2 ± 3.8	6.7 ± 1.5	4.3 ± 0.8	**
Tumor-to-brain ratio	68 ± 30	ND	25 ± 9.2

Results are expressed as PSL/mm² (mean± SD). ND = not detectable, the brain could not be distinguished from the background. **p ≤ 0.001 between [⁶⁸Ga]DOTATOC and [¹⁸F]FDR-NOC in nude mice bearing subcutaneous BT4C tumors.