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18F-Sodium Fluoride PET–CT for the Assessment of Brain Metastasis from Lung Adenocarcinoma

      The optimal treatment of asymptomatic brain metastases (BMs) in non–small-cell lung cancer (NSCLC) patients is still controversial. The role of upfront chemotherapy has not been extensively investigated in randomized clinical trials, mainly because of the belief that blood–brain barrier (BBB) would limit the delivery of cytotoxic drugs. However, platinum-based chemotherapy has reported intracranial response rates ranging from 30% to 45%.
      • Walbert T
      • Gilbert MR
      The role of chemotherapy in the treatment of patients with brain metastases from solid tumors.
      ,
      • Kim KH
      • Lee J
      • Lee JI
      • et al.
      Can upfront systemic chemotherapy replace stereotactic radiosurgery or whole brain radiotherapy in the treatment of non-small cell lung cancer patients with asymptomatic brain metastases?.
      This finding is probably related to the disruption of the BBB in the presence of BMs with consequent penetration of antineoplastic drugs in the tumor tissue. 18F-sodium fluoride (18F-NaF) is a radiopharmaceutical widely used for positron emission tomography–computed tomography (PET–CT) bone scan to detect skeletal metastases. Some cases of unexpected 18F-NaF uptake within BMs from lung cancer, breast cancer, and melanoma have been observed.
      • Li Y
      • Tafti BA
      • Shaba W
      • Berenji GR
      Extraosseus uptake of F-18 fluoride in the primary malignancy and cerebral metastasis in a case of non-small-cell lung cancer.
      ,
      • Wu J
      • Zhu H
      • Ji H
      Unexpected detection of brain metastases by 18F-NaF PET/CT in a patient with lung cancer.
      Furthermore, our research group has recently reported a case series of nine patients with known BMs from different primary tumors, whose intracranial metastases were detectable by 18F-NaF PET-CT.
      • Lunardi G
      • Salgarello M
      • Gorgoni G
      • et al.
      Brain tumours and 18F-NaF PET/CT in patients with different malignancies: A new method for diagnosis?.
      Here, we report a case of a patient with metastatic non–small-cell lung cancer and a single BM treated with upfront chemotherapy, who underwent 18F NaF PET-CT before and after systemic treatment.

      CASE REPORT

      A 57-year-old female former smoker presented with dry cough and chest pain. She had a chest CT scan which demonstrated a 7 cm right upper lobe mass invading mediastinum and anonymous vein. The patient underwent endobronchial ultrasound-guided trans-tracheal needle aspiration of the pulmonary lesion, and pathology examination showed lung adenocarcinoma, with wild-type EGFR and nontranslocated ALK. Abdomen CT scan was negative, whereas head CT scan and MRI showed a 1.2 cm BM in right parietal lobe with surrounding edema (Fig. 1A). The patient had a 18F-NaF PET–CT which showed a lytic metastasis in left iliac bone, and also revealed a 18F-NaF uptake of the BM with SUVmax 4.2 (Fig. 1B, C). The patient was started on chemotherapy with cisplatin (75 mg/m2) and pemetrexed (500 mg/m2) every 3 weeks. The brain MRI performed after two cycles showed a reduction of the BM to 0.9 cm, and the 18F-NaF PET–CT demonstrated a decrease of SUVmax to 2.40 (Fig. 2).
      Figure thumbnail gr1
      FIGURE 1Imaging of brain metastasis before starting systemic therapy. A, Brain MRI showing 12 mm right parietal metastasis with surrounding edema. B, 18F-NaF PET-CT with right parietal brain metastasis uptake 5 minutes after tracer injection; at that time, 18F-NaF is also detectable in the bloodstream within dural venous sinuses. C, 18F-NaF PET-CT 30 minutes after tracer injection; at that time, 18F-NaF is mainly uptaken by cranial bones, but residual uptake of brain metastasis is still detectable. MRI, magnetic resonance imaging; NaF, sodium fluoride; PET–CT, positron emission tomography–computed tomography.
      Figure thumbnail gr2
      FIGURE 2Imaging of brain metastasis after two cycles of cisplatin and pemetrexed. A, Brain MRI showing right parietal metastasis, decreased in size when compared with baseline (9 vs 12 mm, see ). B, 18F-NaF PET-CT performed 5 minutes after tracer injection; the uptake intensity of brain metastasis has decreased from baseline: SUVmax from 4.20 to 2.40 (see ). C, 18F-NaF PET-CT 30 minutes after tracer injection. MRI, magnetic resonance imaging; NaF, sodium fluoride; PET–CT, positron emission tomography–computed tomography.

      DISCUSSION

      This report suggests that in selected patients upfront chemotherapy may achieve an intracranial response. The 18F-NaF uptake of BM has been already reported by other authors.
      • Li Y
      • Tafti BA
      • Shaba W
      • Berenji GR
      Extraosseus uptake of F-18 fluoride in the primary malignancy and cerebral metastasis in a case of non-small-cell lung cancer.
      ,
      • Wu J
      • Zhu H
      • Ji H
      Unexpected detection of brain metastases by 18F-NaF PET/CT in a patient with lung cancer.
      In our patient, consistently with the objective response assessed by MRI, the 18F-NaF SUV decreased of about 50% after two cycles of chemotherapy. However, it is unknown if 18F-NaF is able to provide an estimation of the entity of BBB damage and, moreover, if such damage would be predictive for response of BMs to systemic or local therapy. Accordingly, a prospective clinical trial to investigate the potential role of 18F-NaF PET–CT as a predictive tool for patients with BMs is planned.

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        • Gilbert MR
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        • Lee J
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        Extraosseus uptake of F-18 fluoride in the primary malignancy and cerebral metastasis in a case of non-small-cell lung cancer.
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        Unexpected detection of brain metastases by 18F-NaF PET/CT in a patient with lung cancer.
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        Brain tumours and 18F-NaF PET/CT in patients with different malignancies: A new method for diagnosis?.
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