89Zr-Bevacizumab PET Visualizes Disease Manifestations in Patients with von Hippel–Lindau Disease

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FIGURE 1.
(A) ⁸⁹Zr-bevacizumab PET scan (maximum-intensity projection) of patient 4, demonstrating normal antibody distribution with tracer uptake in blood pool and liver as well as uptake in a hemangioblastoma in cerebellum (SUV_max, 8.3) and in 6 solid kidney lesions (SUV_max, 6.6–27.6). (B) Hemangioblastoma visualized on coronal ⁸⁹Zr-bevacizumab PET, MR, and fusion images (top, middle, and bottom, respectively). (C) Kidney lesion visualized on transversal ⁸⁹Zr-bevacizumab PET, MR, and fusion images (top, middle, and bottom, respectively).
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FIGURE 2.
Number of PET-positive VHL disease manifestations ≥ 10 mm according to germline mutation (A) and SUV_max (B): 1 = c.-89-?_c.297+?del, 2 = c.500G > A, 3 = c.490C > T, 4 = c.509T > A, 5 = c.340 + 1G > A, 6 = c.241C > T, 7 = IVS1-59del46.
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FIGURE 3.
Quantification (median with range) of ⁸⁹Zr-bevacizumab distribution in 22 patients with VHL disease in normal organs and 59 disease manifestations (A) and in VHL disease manifestations according to localization (B).

TABLE 1

Patient Characteristics

	Total population (n = 22)
Characteristic	n	%
Sex
Male	13	59
Female	9	41
Age (y)
Median	42
Range	23–66
Mutation
c.-89-?_c.297+?del	10	45
c.500G > A	5	23
c.509T > A	3	14
c.490C > T	1	5
c.340 + 1G > A	1	5
c.241C > T	1	5
IVS1-59del46 (unclassified variant)	1	5
History
Hemangioblastoma	22	100
Retinal angioma	15	68
Renal cell carcinoma^*	8	36
Pancreatic neuro-endocrine tumor	5	23
Pheochromocytoma	4	18
Prior treatment (no. of patients/procedures)
Craniotomy	12/28	55
Spinal cord hemangioblastoma embolization	2/2	9
Retinal laser/cryotherapy	14/19	64
(Partial) nephrectomy	8/13	36
Adrenalectomy	4/7	18
(Partial) pancreatectomy	2/2	9

↵* One patient had a renal cell carcinoma recurrence on regular surveillance at time written informed consent was given and study imaging was already planned. This patient was motivated for study participation.

TABLE 2

VHL Disease Manifestations on Routine Imaging and on ⁸⁹Zr-Bevacizumab PET Per Patient

Patient no.	Sex	Mutation^*	Age (y)	VHL manifestations^† at baseline anatomic imaging (n)	MRI/CT lesions ≥ 10 mm (n)	PET lesions (n)	SUV_max range
1	Male	1	57	CNS (5), pancreas (2)	2	2	4.8–6.0
2	Female	1	23	CNS (1)	1	0
3	Male	1	31	CNS (8), kidney (1), epididymis^‡ (1)	3	1	12.2
4	Male	4	61	CNS (4), kidney (8), pancreas (1)	10	7	6.6–27.6
5	Female	2	61	CNS (13), kidney (3), pancreas (1)	9	8	2.4–28.3
6	Male	1	62	CNS (3), pancreas (2)	3	1	6.7
7	Female	1	36	CNS (19), pancreas (2)	3	3	1.3–2.8
8	Female	1	29	CNS (10), pancreas (1)	2	1	1.4
9	Male	7	33	CNS (2), pancreas (2)	1	1	4.3
10	Female	2	48	CNS (9), kidney (4), pancreas (1)	5	1	1.6
11	Female	1	29	CNS (7)	1	1	1.6
12	Female	2	38	CNS (4), pancreas (1), adrenal gland (1)	1	2	4.1–6.4
13	Male	1	63	CNS (4), kidney (4), pancreas (1)	3	0
14	Female	3	46	CNS (1), pancreas (1)	1	0
15	Female	1	60	CNS (1), pancreas (1), liver (100), bone^¶ (1)	81	18	5.7–15.4
16	Male	2	26	CNS (3)	1	0
17	Male	5	32	CNS (8), kidney (2), pancreas (1)	3	3	4.3–35.8
18	Male	1	31	CNS (7)	0	0
19	Male	3	50	CNS (55), epididymis^‡ (1)	5	7	2.7–9.0
20	Male	2	46	CNS (1)	1	0
21	Male	3	66	CNS (4)	2	2	3.4–5.7
22	Male	6	35	CNS (1), kidney (1)	1	1	26.6

↵* Mutation, 1 = c.-89-?_c.297+?del, 2 = c.490C > T, 3 = c.500G > A, 4 = c.509T > A, 5 = c.340 + 1G > A, 6 = c.241C > T, 7 = IVS1–59del46 (unclassified variant).
↵† Excluding simple cysts.
↵‡ Demonstrated on ultrasound.
↵¶ Demonstrated on ¹¹C-hydroxytryptophan PET and MRI.

TABLE 3

VHL Disease Manifestations^* on Routine Imaging and on ⁸⁹Zr-Bevacizumab PET Per Organ

↵* Not including simple cysts.
↵† Liver metastases of pancreatic neuroendocrine tumor.
↵‡ Ultrasound-confirmed cystadenomas.
↵¶ Pelvic bone metastasis of pancreas neuroendocrine tumor ¹¹C-5-hydroxytryptophan PET and MRI confirmed.