Advanced

18 F-fluoride as a prognostic indicator of bone regeneration

Mathavan, Neashan LU ; Koopman, Janine LU ; Raina, Deepak Bushan LU ; Turkiewicz, Aleksandra LU ; Tägil, Magnus LU and Isaksson, Hanna LU (2019) In Acta Biomaterialia 90. p.403-411
Abstract


Positron emission tomography (PET) is a form of nuclear imaging, which quantitatively assesses the metabolic activity through the uptake of radioactive tracers.
18
F-fluoride is a positron-emitting isotope with high affinity for bone. Despite its potential as a non-invasive measure of bone metabolism, quantitative
18
F-fluoride PET has only been used sparsely in orthopaedic applications. It has been speculated... (More)


Positron emission tomography (PET) is a form of nuclear imaging, which quantitatively assesses the metabolic activity through the uptake of radioactive tracers.
18
F-fluoride is a positron-emitting isotope with high affinity for bone. Despite its potential as a non-invasive measure of bone metabolism, quantitative
18
F-fluoride PET has only been used sparsely in orthopaedic applications. It has been speculated that
18
F-fluoride PET characterizes cellular activity of bone forming cells in the early stages of the regenerative process and therefore precedes the mineralization detected by conventional computed tomography (CT). Our aim was thus to combine in vivo PET and CT to map the spatiotemporal course of bone regeneration during fracture healing using an open femur fracture model in the rat and characterize regeneration in untreated and pharmacologically treated fractures using both imaging modalities. We hypothesized that PET
18
F-fluoride tracer activity at an earlier time point is predictive of CT measured bone formation at a later time point. On the basis of the RMSE and R
2
metrics of linear regression models it was conceivable for bone volumes to be predicted up to three weeks in advance in a rodent model (RMSE: 14 mm
3
–18 mm
3
, R
2
: 0.79–0.82). Moreover, the data suggested that
18
F-fluoride positron-emitting activity had the potential to separate bone formation from resorption and thus could be of interest across a wide array of orthopaedic applications. Based on this data, we conclude that
18
F-fluoride positron-emitting activity is strongly correlated to bone formation and could potentially predict the volume of bone regenerated at fracture sites. The volume of bone regenerated at a fracture site can be interpreted as a measure of the healing response and
18
F-fluoride should be further investigated as a predictive diagnostic tool to identify if bone fractures will heal successfully or result in delayed healing or non-union. Statement of Significance: We aimed to combine in vivo PET and CT imaging to map the spatiotemporal course of bone regeneration during fracture healing using an open femur fracture model in the rat and characterize regeneration in untreated and pharmacologically treated fractures using both imaging modalities. We hypothesized that PET
18
F-fluoride tracer activity at an earlier time point is predictive of CT measured bone formation at a later time point. Our data suggest that
18
F-fluoride positron-emitting activity can separate bone formation from resorption and thus could be of interest across a wide array of orthopaedic applications including as a predictive diagnostic tool to identify if fractures will heal successfully or result in delayed healing or non-union.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
18F, Bone formation, Bone healing, CT, Fracture repair, PET, Positron emission tomography
in
Acta Biomaterialia
volume
90
pages
403 - 411
publisher
Elsevier
external identifiers
  • scopus:85064264729
ISSN
1742-7061
DOI
10.1016/j.actbio.2019.04.008
language
English
LU publication?
yes
id
afb60212-43e6-4dd7-a02f-bbf2ddffd205
date added to LUP
2019-04-25 14:21:24
date last changed
2019-07-01 12:13:15
@article{afb60212-43e6-4dd7-a02f-bbf2ddffd205,
  abstract     = {<p><br>
                                                         Positron emission tomography (PET) is a form of nuclear imaging, which quantitatively assesses the metabolic activity through the uptake of radioactive tracers.                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride is a positron-emitting isotope with high affinity for bone. Despite its potential as a non-invasive measure of bone metabolism, quantitative                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride PET has only been used sparsely in orthopaedic applications. It has been speculated that                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride PET characterizes cellular activity of bone forming cells in the early stages of the regenerative process and therefore precedes the mineralization detected by conventional computed tomography (CT). Our aim was thus to combine in vivo PET and CT to map the spatiotemporal course of bone regeneration during fracture healing using an open femur fracture model in the rat and characterize regeneration in untreated and pharmacologically treated fractures using both imaging modalities. We hypothesized that PET                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride tracer activity at an earlier time point is predictive of CT measured bone formation at a later time point. On the basis of the RMSE and R                             <br>
                            <sup>2</sup><br>
                                                          metrics of linear regression models it was conceivable for bone volumes to be predicted up to three weeks in advance in a rodent model (RMSE: 14 mm                             <br>
                            <sup>3</sup><br>
                                                         –18 mm                             <br>
                            <sup>3</sup><br>
                                                         , R                             <br>
                            <sup>2</sup><br>
                                                         : 0.79–0.82). Moreover, the data suggested that                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride positron-emitting activity had the potential to separate bone formation from resorption and thus could be of interest across a wide array of orthopaedic applications. Based on this data, we conclude that                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride positron-emitting activity is strongly correlated to bone formation and could potentially predict the volume of bone regenerated at fracture sites. The volume of bone regenerated at a fracture site can be interpreted as a measure of the healing response and                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride should be further investigated as a predictive diagnostic tool to identify if bone fractures will heal successfully or result in delayed healing or non-union. Statement of Significance: We aimed to combine in vivo PET and CT imaging to map the spatiotemporal course of bone regeneration during fracture healing using an open femur fracture model in the rat and characterize regeneration in untreated and pharmacologically treated fractures using both imaging modalities. We hypothesized that PET                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride tracer activity at an earlier time point is predictive of CT measured bone formation at a later time point. Our data suggest that                              <br>
                            <sup>18</sup><br>
                                                         F-fluoride positron-emitting activity can separate bone formation from resorption and thus could be of interest across a wide array of orthopaedic applications including as a predictive diagnostic tool to identify if fractures will heal successfully or result in delayed healing or non-union.                         <br>
                        </p>},
  author       = {Mathavan, Neashan and Koopman, Janine and Raina, Deepak Bushan and Turkiewicz, Aleksandra and Tägil, Magnus and Isaksson, Hanna},
  issn         = {1742-7061},
  keyword      = {18F,Bone formation,Bone healing,CT,Fracture repair,PET,Positron emission tomography},
  language     = {eng},
  pages        = {403--411},
  publisher    = {Elsevier},
  series       = {Acta Biomaterialia},
  title        = {<sup>18</sup>
                                                 F-fluoride as a prognostic indicator of bone regeneration},
  url          = {http://dx.doi.org/10.1016/j.actbio.2019.04.008},
  volume       = {90},
  year         = {2019},
}