|Year : 2015 | Volume
| Issue : 3 | Page : 652
The effect of bevacizumab for bone scintigraphy imaging: A case report
Takamitsu Asano, Osamu Takakuwa, Ken Maeno, Tetsuya Oguri, Akio Niimi
Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan
|Date of Web Publication||9-Oct-2015|
Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya
Source of Support: None, Conflict of Interest: None
A 65-year-old man presented with pulmonary nodules and a right humeral fracture. The 99mTc-hydroxy-methylene-diphosphonate (HMDP) bone scintigraphy showed high-intensity radioisotope (RI) uptake by a tumor of the right arm. Adenocarcinoma of the lung with an epidermal growth factor receptor (EGFR) mutation was diagnosed on pathological examination of the computed tomography (CT)-guided needle biopsy of the right humerus. Although, gefitinib therapy was initiated, the tumor progressed. The patient was then treated with second-line chemotherapy including bevacizumab. The CT scan showed a new bone metastasis in the ilium and right sacroiliac articulation. However, this new bone metastasis was not detected by HMDP-bone scintigraphy. Physicians should be wary of the interpretations of the findings of the 99mTc HMDP bone scintigraphy after the bevacizumab treatment.
Keywords: Bevacizumab, bone scintigraphy, EGFR mutation, non-small cell lung cancer
|How to cite this article:|
Asano T, Takakuwa O, Maeno K, Oguri T, Niimi A. The effect of bevacizumab for bone scintigraphy imaging: A case report. J Can Res Ther 2015;11:652
| > Introduction|| |
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has been shown to benefit patients with non-small-cell lung cancer (NSCLC).  Several reports have demonstrated that bevacizumab could affect the findings of imaging examinations including positron emission tomography (PET) and magnetic resonance imaging (MRI). , However, the effects of bevacizumab on the findings of bone scintigraphy have not been reported. A case of NSCLC in which bone scintigraphy differed before and after treatment with bevacizumab is reported.
| > Case repor|| |
A 65-year-old man with pain in the right shoulder joint was referred to our hospital and was diagnosed as having a right caput humeri fracture on chest X-ray. Computed tomography (CT) of the lesion showed an osteolytic tumor suggestive of metastasis [Figure 1]a, a nodule in the upper lobe of the left lung, and multiple hypodense masses in the liver. The 99mTc-hydroxy-methylene-diphosphonate (HMDP) bone scintigraphy showed high-intensity radioisotope (RI) uptake by the tumor of the right arm [Figure 1]b. On pathological examination of samples obtained by CT-guided needle biopsy of the caput humeri lesion, a diagnosis of metastasis of lung adenocarcinoma with an exon 21 L858R mutation of the epidermal growth factor receptor (EGFR) was made.
|Figure 1: (a) Chest computed tomography shows an osteolytic tumor of the right upper humerus (Allow head) (b) 99mTc HMDP bone scintigraphy shows high-intensity uptake in the tumor of the right upper humerus (Allow head) (c) Chest computed tomography scan shows an osteolytic tumor at the ilium and right sacroiliac articulation (Allow head) (d) 99mTc HMDP bone scintigraphy shows no evidence of an osteolytic tumor at the ilium and right sacroiliac articulation|
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Gefitinib was started as first-line chemotherapy, but liver metastases enlarged after three weeks of treatment. Then, carboplatin (AUC6), paclitaxel (200 mg/m 2 ), and bevacizumab (15 mg/kg) was given as second-line chemotherapy. Since a partial response (PR) was achieved, this regimen was continued for six cycles, followed by maintenance therapy with bevacizumab. After two cycles of the maintenance therapy, the patient developed pelvic pain on walking. CT scan showed a new metastatic tumor in the ilium and right sacroiliac articulation [Figure 1]c. The 99mTc HMDP bone scintigraphy was done immediately, but the scintigraphy did not show the presence of tumor [Figure 1]d. With respect to the right humeral metastasis, RI uptake was also decreased compared to imaging before treatment. Third-line chemotherapy consisting of pemetrexed and radiation therapy for the bone metastasis lesion was then performed, but the patient died of cancer progression three months later.
| > Discussion|| |
Anti-angiogenesis is a promising antitumor strategy that inhibits tumor vascular formation to suppress tumor growth.  Recently, bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to be beneficial for cancer treatment, including nonsquamous NSCLC.  Bevacizumab provides normalization of abnormal tumor vasculature by pruning immature vessels and improving integrity and function of the remaining vasculature,  which improves the delivery of subsequent chemotherapy  and then enhances the anticancer effect. Meanwhile, some reports have demonstrated that treatment with bevacizumab resulted in changes of imaging tests because of its anti-angiogenic effect. That is, bevacizumab could cause misleading PET findings due to the osteoblastic flare phenomenon  and alter the typical patterns of blood-brain barrier breakdown and permeability of surrounding tumor vasculature seen with cerebral metastases on head MRI. 
Bone scintigraphy is considered one of the most sensitive methods of evaluation and provides information on the presence and localization of skeletal metastases.  The specificity of bone scintigraphy is reported to be 98%, and, otherwise, the sensitivity remains approximately 70%.  Uptake of labelled 99mTc HMDP depends not only on local blood flow, but also on local osteoblastic activity. Therefore, some tumor features, such as being highly anaplastic and slow growing, could also contribute to the difficulty in detection.  In the present case, 99mTc HMDP bone scintigraphy at the time of diagnosis clearly demonstrated the bone metastasis of the right caput humeri.
In contrast, 99mTc HMDP bone scintigraphy did not demonstrate the bone metastasis at relapse. Therefore, it seems unlikely that the original features of the tumor explain the discrepancy. The radiopharmaceutical, 99mTc HMDP, reaches the osseous structures by way of the vascular system, and it has been reported that alterations of blood supply or bone blood flow change the amount of material reaching that area.  Thus, the possibility that the effect of bevacizumab on tumor vasculature , affected the findings of bone scintigraphy can be considered.
A case of NSCLC in which bone scintigraphy showed differences in the imaging findings for bone metastasis before and after treatment with bevacizumab was presented. Physicians should be wary of the interpretations of findings of 99mTc HMDP bone scintigraphy during bevacizumab treatment.
| > References|| |
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al
. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355:2542-50.
Mathews MS, Linskey ME, Hasso AN, Fruehauf JP. The effect of bevacizumab (Avastin) on neuroimaging of brain metastases. Surg Neurol 2008;70:649-52.
Krupitskaya Y, Eslamy HK, Nguyen DD, Kumar A, Wakelee HA. Osteoblastic bone flare on F18-FDG PET in non-small cell lung cancer (NSCLC) patients receiving bevacizumab in addition to standard chemotherapy. J Thorac Oncol 2009;4:429-31.
Chen CT, Hung MC. Beyond anti-VEGF: Dual-targeting antiangiogenic and antiproliferative therapy. Am J Transl Res 2013;5:393-403.
Tong RT, Boucher Y, Kozin SV, Winkler F, Hicklin DJ, Jain RK. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res 2004;64:3731-6.
Jain RK. Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science 2005;307:58-62.
Cook GJ, Fogelman I. The role of nuclear medicine in monitoring treatment in skeletal malignancy. Semin Nucl Med 2001;31:206-11.
Eustace S, Tello R, DeCarvalho V, Carey J, Wroblicka JT, Melhem ER, et al.
A comparison of whole-body turboSTIR MR imaging and planar 99mTc-methylene diphosphonate scintigraphy in the examination of patients with suspected skeletal metastases. AJR Am J Roentgenol 1997;169:1655-61.
O′Mara RE. Skeletal scanning in neoplastic disease. Cancer 1976;37:480-86.