Case Report
Nuclear Medicine
June 2006

Flare Response in 18F-Fluoride Ion PET Bone Scanning

We report a case of osseous flare response in the thoracic spine, correlating its appearance on 18F-FDG and 18F-fluoride ion PET, CT, technetium-99m medronate (99mTc-MDP) bone scanning, and gadolinium-enhanced MRI. Osteoblastic flare phenomenon has been described in detail using 99mTc-MDP scintigraphy [1]. The flare response refers to an increase in uptake after the initiation of therapy, corresponding with sites of osteoblastic activity at treated metastases.
Planar 18F-fluoride ion scintigraphy [2] was largely abandoned in favor of 99mTc-MDP for metastatic evaluation of the skeleton because of its more favorable photon energies for whole-body gamma camera imaging. However, after the inception of cross-sectional 18F-fluoride ion PET [3], the increasing availability of PET has renewed interest in this agent because of its increased spatial resolution and contrast and, thus, its increased sensitivity compared with planar imaging or SPECT with diphosphonates [4].
Fig. 1A —27-year-old woman with breast cancer. Staging CT scan (A) and follow-up CT scan after change of therapy (B) at T7 show sclerotic changes that appear after change of therapy.
Fig. 1B —27-year-old woman with breast cancer. Staging CT scan (A) and follow-up CT scan after change of therapy (B) at T7 show sclerotic changes that appear after change of therapy.
Fig. 1C —27-year-old woman with breast cancer. Sagittal T1 images of thoracic spine obtained before (C) and after (D) gadolinium administration show corresponding enhancing lesion at T7.
Fig. 1D —27-year-old woman with breast cancer. Sagittal T1 images of thoracic spine obtained before (C) and after (D) gadolinium administration show corresponding enhancing lesion at T7.
Fig. 1E —27-year-old woman with breast cancer. After change of therapy, sagittal T1 images of thoracic spine obtained before (E) and after (F) gadolinium administration show enhancement has resolved.
Fig. 1F —27-year-old woman with breast cancer. After change of therapy, sagittal T1 images of thoracic spine obtained before (E) and after (F) gadolinium administration show enhancement has resolved.
Fig. 1G —27-year-old woman with breast cancer. Technetium-99m medronate (99mTc-MDP) bone scans on initial staging (G) and after change of therapy (H) show no uptake at T7 on initial staging and mildly increased uptake at T7 after change of therapy, respectively.
Fig. 1H —27-year-old woman with breast cancer. Technetium-99m medronate (99mTc-MDP) bone scans on initial staging (G) and after change of therapy (H) show no uptake at T7 on initial staging and mildly increased uptake at T7 after change of therapy, respectively.
Fig. 1I —27-year-old woman with breast cancer. 18F-fluoride ion PET scan (I) obtained soon after MRI shows increased uptake at T7, which was not evident on initial MDP bone scan; follow-up examination after change of therapy (J) shows interval increase in uptake.
Fig. 1J —27-year-old woman with breast cancer. 18F-fluoride ion PET scan (I) obtained soon after MRI shows increased uptake at T7, which was not evident on initial MDP bone scan; follow-up examination after change of therapy (J) shows interval increase in uptake.
Fig. 1K —27-year-old woman with breast cancer. Coronal image from 18F-FDG PET (K) shows increased uptake at T7; follow-up examination after institution of effective therapy (L) shows photopenia at T7, compatible with the decrease in metabolic activity associated with treatment of the metastatic lesion.
Fig. 1L —27-year-old woman with breast cancer. Coronal image from 18F-FDG PET (K) shows increased uptake at T7; follow-up examination after institution of effective therapy (L) shows photopenia at T7, compatible with the decrease in metabolic activity associated with treatment of the metastatic lesion.

Case Report

A 27-year-old woman was initially diagnosed with infiltrating ductal carcinoma of the right breast in her third trimester of pregnancy. Excisional biopsy revealed a 2.5-cm grade II/III carcinoma with positive margins. Because of her pregnancy, imaging studies were not performed before initiation of chemotherapy. She was begun immediately on systemic therapy with cyclophosphamide and doxorubicin with the plan of completing four cycles before reexcision and lymph node dissection. She delivered a healthy baby before her second cycle of chemotherapy, which was given on schedule. After delivery she underwent her initial staging examinations including abdominopelvic and chest CT and MDP bone scanning. These examinations showed no evidence of metastatic disease (Figs. 1A and 1G).
The patient completed the last two cycles of cyclophosphamide and doxorubicin as planned and proceeded to definitive surgery. There was a small focus of residual carcinoma in the breast, but unfortunately carcinoma was found in 21 of the 22 axillary lymph nodes resected. Because of this finding and her young age, it was decided to restage the cancer using the most sensitive technique available: PET/CT.
Thus, the patient underwent FDG PET/CT two and a half months after her baseline staging studies. Multiple foci of elevated FDG uptake corresponding with mediastinal and hilar adenopathy were shown. A focus of elevated fluoride ion and FDG uptake in the T7 vertebral body (Figs. 1I and 1K) was shown on MRI to be an enhancing lesion diffusely involving and replacing this vertebral body (Figs. 1C and 1D). Bronchoscopy and mediastinoscopy showed multiple nodal metastases at this time.
The patient was treated with leuprolide and an aromatase inhibitor and begun on capecitabine as systemic therapy. Monthly zoledronate therapy was also initiated. After receiving three cycles (9 weeks) of capecitabine, an FDG PET scan showed resolution of the uptake in the mediastinum and T7. After four more cycles (12 weeks) of capecitabine, repeat imaging was performed including 18F-fluoride ion bone scanning, 18F-FDG PET/CT, MRI of the spine, and subsequently 99mTc-MDP bone scanning. Fluoride ion bone scanning showed increased uptake in T7, which was photopenic on FDG PET and sclerotic on CT. MRI of the spine confirmed a decrease in enhancement at this location. There was also a subtle interval increase in uptake at T7 on the 99mTc-MDP bone scans.

Discussion

In this case, several aspects of ongoing treatment were assessed using multiple techniques to form a cohesive conclusion. Correlation of the imaging findings suggests a healing response after treatment: The increased activity at T7 on the 18F-fluoride study after change in therapy is compatible with increased bone turnover [5]; and the FDG PET study suggests decreased metabolic activity, which was confirmed by anatomic information provided by CT (sclerosis) and MRI (decreased interval enhancement). Taken together, these findings are most suggestive of a flare response—that is, increase in bone repair after successful treatment of metastasis. Notably, the 99mTc-MDP bone scans obtained before and after treatment (Figs. 1G and 1H) showed a similar, but less obvious, increase in uptake at the T7 focus compared with the fluoride ion study, further showing the greater sensitivity and resolution of the PET evaluation (fluoride) as compared with the single-photon evaluation (MDP) of osteoblastic activity.
In treated osseous breast cancer metastases, an increase in activity (i.e., an osteoblastic flare response) is the rule rather than the exception. Up to 75% of patients with breast cancer show increased activity or new lesions due to bone repair at responding sites of metastasis [1], with a subsequent decrease in activity 6 months later. A decrease in FDG uptake and increase in MDP uptake, similar to the case shown here, have also been described in prostate cancer flare response [6].
In summary, our case provides a comprehensive radiologic depiction of the appearance of the osteoblastic flare response in a patient treated for metastatic breast cancer. The superior contrast and resolution of the 18F-fluoride ion PET scan provides a more sensitive diagnostic tool than does MDP scanning, while correlative FDG imaging adds diagnostic specificity.

Footnote

Address correspondence to A. A. Wade.

References

1.
Coleman RE, Mashiter G, Whitaker KB, Moss DW, Rubens RD, Fogelman I. Bone scan flare predicts successful systemic therapy for bone metastases. J Nucl Med 1988; 29:1354-1359
2.
Blau M, Nagler W, Bender MA. Fluorine-18: a new isotope for bone scanning. J Nucl Med 1962; 3:332-334
3.
Hoh CK, Hawkins RA, Dahlborn M, et al. Whole body skeletal imaging with [18F]fluoride ion and PET. J Comput Assist Tomogr 1993; 17:34-41
4.
Schirrmeister H, Guhlmann A, Elsner K, et al. Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET. J Nucl Med 1999; 40:1623-1629
5.
Cook GJ, Fogelman I. The role of positron emission tomography in the management of bone metastases. Cancer 2000; 88:2927-2933
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Shimizu N, Masud H, Yamanaka H, Oriuchi N, Inoue T, Endo K. Fluorodeoxyglucose positron emission tomography scan of prostate cancer bone metastases with flare reaction after endocrine therapy. J Urol 1999; 161:608-609

Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 1783 - 1786
PubMed: 16714674

History

Submitted: February 9, 2005
Accepted: March 14, 2005

Keywords

  1. breast cancer
  2. oncologic imaging
  3. PET/CT
  4. spine
  5. vertebral column

Authors

Affiliations

Andrew A. Wade
Department of Radiology, Massachusetts General Hospital, 55 Fruit St., FND 216 Boston, MA 02114.
James A. Scott
Department of Radiology, Massachusetts General Hospital, 55 Fruit St., FND 216 Boston, MA 02114.
Irene Kuter
Department of Hematology and Oncology, Massachusetts General Hospital, Boston, MA 02114.
Alan J. Fischman
Department of Radiology, Massachusetts General Hospital, 55 Fruit St., FND 216 Boston, MA 02114.

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