Kinetic analysis of 18F-fluoride PET images of breast cancer bone metastases

Abstract

The most common site of metastasis for breast cancer is bone. Quantitative (18)F-fluoride PET can estimate the kinetics of fluoride incorporation into bone as a measure of fluoride transport, bone formation, and turnover. The purpose of this analysis was to evaluate the accuracy and precision of (18)F-fluoride model parameter estimates for characterizing regional kinetics in metastases and normal bone in breast cancer patients.

Methods: Twenty metastatic breast cancer patients underwent dynamic (18)F-fluoride PET. Mean activity concentrations were measured from serial blood samples and regions of interest placed over bone metastases, normal vertebrae, and cardiac blood pools. This study examined parameter identifiability, model sensitivity, error, and accuracy using parametric values from the patient cohort.

Results: Representative time-activity curves and model parameter ranges were obtained from the patient cohort. Model behavior analyses of these data indicated (18)F-fluoride transport and flux (K(1) and Ki, respectively) into metastatic and normal osseous tissue could be independently estimated with a reasonable bias of 9% or less and reasonable precision (coefficients of variation <or= 16%). Average (18)F-fluoride transport and flux into metastases from 20 patients (K(1) = 0.17 +/- 0.08 mL x cm(-3) x min(-1) and Ki = 0.10 +/- 0.05 mL x cm(-3) x min(-1)) were both significantly higher than for normal bone (K(1) = 0.09 +/- 0.03 mL x cm(-3) x min(-1) and Ki = 0.05 +/- 0.02 mL x cm(-3) x min(-1), P < 0.001).

Conclusion: Fluoride transport and flux can be accurately and independently estimated for bone metastases and normal vertebrae. Reasonable bias and precision for estimates of K(1) and Ki from simulations and significant differences in values from patient modeling results in metastases and normal bone suggest that (18)F-fluoride PET images may be useful for assessing changes in bone turnover in response to therapy. Future studies will examine the correlation of parameters to biologic features of bone metastases and to response to therapy.

FIGURE 1

Sagittal ¹⁸F-fluoride images (left) and ¹⁸F-FDG images (right) for 2 patients exhibiting bone-dominant breast cancer metastases (arrowheads). (A) First patient (top) has primarily sclerotic tumor that is clearly visible in ¹⁸F-fluoride image. (B) Second patient (bottom) has lytic tumor that is evident as photopenic region in ¹⁸F-fluoride image and enhanced region in ¹⁸F-FDG image.

FIGURE 2

Sensitivity functions representing time-dependent percentage change in model output resulting from ±1% change in parameters K₁ (solid line), V_D (crosses), k₃ (△), and k₄ (◊) are shown for axial breast cancer bone metastases (A) and normal bone vertebrae (B).

FIGURE 3

Quantile box plots of ¹⁸F-fluoride modeling results for 20 patients with breast cancer bone metastases. Tumor results appear in left panels and normal bone in right panels for 4 floating model parameters (K₁ [A], V_D [B], k₃ [C], and k₄ [D]) and for flux macroparameter, Ki (E). Top, middle, and bottom box lines in plots represent 75th, 50th, and 25th percentiles, whereas extent of vertical lines shows range of parameter values.

FIGURE 4

Model parameter correlation plots of ¹⁸F-fluoride flux, Ki, vs. transport, K₁, for 20 axial breast cancer bone metastases classified from CT analysis to be either lytic (crosses), sclerotic (○), or unknown (△) (A) and normal bone vertebrae (B). Filled circles (●) identify 2 patients whose chemotherapy changed less than 3 mo before their PET scan. Arrow indicates lytic tumor identified in Figure 1B.