SKELETAL IMAGING WITH 18 F-FLUORIDE PET. Frederick D. Grant, M.D. Children s Hospital, Boston Harvard Joint Program in Nuclear Medicine

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SKELETAL IMAGING WITH 18 F-FLUORIDE PET Frederick D. Grant, M.D. Children s Hospital, Boston Harvard Joint Program in Nuclear Medicine

Bone Imaging Agents kev T 1/2 Imaging Delay Year Sr-85 514 65 d 3-7 d 1961 Sr-87m 388 2.8 h (1-3 h) 1969 F-18 sodium fluoride (511) 1.8 h 0.5 1 h 1962 Tc-99m phosphates 140 6 h 4-6 h 1971 Tc-99m diphosphonates 140 6 h 3 h 1973

LOG % ADMINISTERED ACTIVITY IN BLOOD 100 50 10 5 2 4 6 TIME (HRS) BLOOD CLEARANCE OF SKELETAL IMAGING AGENTS Strontium (t 1/2 18-24 h) Polyphosphate (t 1/2 8.1 h) Pyrophosphate (t 1/2 10.5 h) Diphosphonate (t 1/2 3.2 h) Fluoride (t 1/2 1.3 h) ADAPTED FROM: Blau et al. JNM 1962 AND Ackerhalt, Slides are et not to al. be reproduced JNM without 1973.

Skeletal Imaging with 18 F-NaF PET 18 F-sodium fluoride approved by FDA in 1972 Gamma camera imaging of 511 kev photons Rapidly replaced by 99m Tc-diphosphonates Anger camera optimized for 140 kev generator production of 99m Tc availability of 99m Tc bone agent kits With clinical adoption of PET imaging PET cameras now widely available 18 F shipping logistics improved Re-visit use of 18 F-NaF for bone imaging

Skeletal Imaging: Utility of 18 F-NaF PET Primary osseus tumors Skeletal metastases Benign skeletal disease Sports Medicine Fractures Other indications? Concerns and Issues

8 year-old boy with Ewing s sarcoma 18 F-NaF 99m Tc-MDP

Imaging skeletal metastases 99m Tc-MDP planar scintigraphy 99m Tc-MDP SPECT 18 F-NaF PET COURTESY Abass Alavi, M.D.

Detecting Skeletal Metastases with 18 F-NaF PET 99m Tc-MDP SPECT is more sensitive than planar SPECT, not planar, 99m Tc-MDP imaging is the appropriate comparison for 18 F-NaF PET 18 F-NaF PET vs. 99m Tc-MDP SPECT 18 F-NaF PET is more sensitive 18 F-NaF PET has higher image quality 18 F-NaF PET and 99m Tc-MDP SPECT have similar specificities Both 18 F-NaF PET and 99m Tc-MDP SPECT need correlative imaging

Bone Imaging with PET WITH PERMISSION Langsteter, et al. Semin Nucl Slides Med. are not 2006 to be reproduced without

Imaging Skeletal Metastases: 18 F-NaF and 18 F-FDG PET 18 F-NaF and 18 F-FDG both have higher sensitivity than 99m Tc-MDP 18 F-FDG more likely to detect: non-osseous disease bone marrow metastases small lytic lesions 18 F-NaF is specific for cortical bone involvement 18 F-NaF more likely to detect: tumors with low FDG avidity

Initial 12 weeks later 18 F-NaF PET 27 year-old woman receiving chemotherapy for metastatic breast carcinoma 18 F-FDG PET

Initial 12 weeks later 18 F-NaF PET Flare response in vertebra T7 after 4 cycles of chemotherapy for breast cancer Alan Fischman, et al. Massachusetts General Hospital 18 F-FDG PET

2 year-old girl with neuroblastoma

18 F-NaF Bone Imaging: Sports Medicine 18 year-old female runner Training for a marathon Severe lower leg and foot pain

18 F-NaF Bone Imaging: Sports Medicine 18 year-old female runner Training for a marathon Severe lower leg and foot pain Scan completed ~1 hour after arrival in Nuclear Medicine Widespread stress injury in both tibiae, right fibula, both feet

18 F-NaF Bone Imaging: Sports Medicine 12 year-old gymnast with lower back pain

18 F-NaF Bone Imaging: Sports Medicine 12 year-old gymnast with lower back pain Left pars stress in vertebra L5

18 F-NaF Bone Imaging: Sports Medicine 21 year-old runner with lower back pain

18 F-NaF Bone Imaging: Sports Medicine 21 year-old runner with lower back pain Increased uptake left sacro-iliac joint, likely stress injury

18 F-NaF Bone PET: CT co-registration 17 year-old male athlete with lower back pain that worsens with hyperextension Increased F-18 uptake suggests right pars stress in vertebra L5 Corresponds to a nondisplaced pars fracture

18 F-NaF Bone PET: CT co-registration 15 year-old female athlete with back pain after landing from a high jump Increased F-18 uptake corresponds to a wedge compression fracture of vertebra L3

Detecting Skeletal Metastases with 18 F-NaF PET/CT Specificity of 18 F-NaF PET improved by CT 18 F-NaF PET/CT has higher specificity than 99m Tc-MDP SPECT BUT: 99m Tc-MDP SPECT is changing improved image processing (software) how will 99m Tc-MDP SPECT/CT perform? 18 F-NaF PET/CT typically not head-to-toe

Non-accidental Trauma / Child Abuse 3 month old boy brought to ED by his mother; she reports that the child is not using his right arm after an older sibling pushed him off a bed

Non-accidental Trauma / Child Abuse Multiple sites of uptake corresponding to fractures on skeletal survey. 18 F-NaF bone PET improves sensitivity and specificity of skeletal survey.

18 F-NaF Bone PET: Other Indications Femoral head osteonecrosis Bone graft viability Quantitative bone turnover studies Three-phase bone scan??

18 F-NaF Skeletal PET: Concerns and Issues Dosimetry Departmental Workflow Reimbursement

18 F-NaF Skeletal PET: Dosimetry compared to 99m Tc-MDP Radiation 18 F: positron (local) + 511keV gamma 99m Tc: 140 kev gamma Physical Half-life 18 F: 110 minutes 99m Tc: 6 hours Bone Uptake and Soft Tissue Clearance Both have ~50% uptake in bone 18 F soft tissue clearance faster than 99m Tc-MDP

18 F-NaF Skeletal PET: Dosimetry compared to 99m Tc-MDP 70 kg Adult Administered Dose (mci) (MBq) Effective Dose (msv) Bladder Wall (mgy) Bone surfaces (mgy) Red Marrow (mgy) 99m Tc-MDP 14 518 3.0 24.9 32.6 4.8 18 F-NaF 4 148 4.0 32.6 5.9 5.9 F. Fahey IN Grant, et al. JNM 2008

18 F-NaF PET vs. 99m Tc-MDP : Age-Dependent Effective Dose (msv) Age (y) Weight (kg) 99m Tc-MDP (0.2 mci/kg) 18 F-NaF (0.06 mci/kg) Adult 70 3.0 4.0 15 55 2.8 3.9 10 32 2.6 3.5 5 19 2.0 3.4 1 9.8 2.0 3.6 F. Fahey IN Grant, et al. JNM 2008.

18 F-NaF Skeletal PET: Concerns and Issues Dosimetry Departmental Workflow Reimbursement

99m Tc-MDP Uptake Imaging 18 F-NaF 1 2 3 4 (hr) Imaging Workflow with 18 F-NaF faster turnaround than 99m Tc-MDP facilitates same day follow-up requires PET scanner availability Image Acquisition with 18 F-NaF less patient motion with faster PET scan no motion correction with PET sedation of very young children

18 F-NaF Skeletal PET: Concerns and Issues Dosimetry Departmental Workflow Reimbursement Depends on insurance company Very difficult if SPECT is a struggle Separate CPT code might facilitate Probably the biggest hurdle to the routine use of 18 F-NaF bone scans

Indications for 18 F-Fluoride Skeletal PET Oncology Skeletal metastatic disease Identification Assessing response to therapy Bone pain in cancer patients Primary bone tumors Benign Bone Disease Sports Medicine (back, extremities) Fractures Others?

Bone Imaging with 18 F-NaF Skeletal PET Higher quality images than 99m Tc-MDP SPECT, with similar radiation dose Potential for improved workflow More accurate than 99m Tc-MDP SPECT in detecting both benign and metastatic skeletal disease Unresolved Questions: How will 99m Tc-MDP SPECT/CT compare? Will reimbursement issues be resolved?