Overview
Bone-specific SPECT tracer:
Bone-specific and non-specific PET tracers:
- 18F-Fluoride
- 18F-FDG
- 18F-Choline
- 68Ga-PSMA and 18F-PSMA
Current evidence
Advantages of SPECT and SPECT-CT (Figure 1)
Similar to planar scintigraphy, SPECT utilises gamma-ray, both these modalities are highly sensitive, widely available and relatively cheap to conduct. Compared to planar scintigraphy which has poor spatial resolution (1 cm), SPECT-CT is able to more accurately localise metabolically active foci and characterise them, reducing equivocal reports and allows reliable identification of degenerative disease, often difficult to be distinguished from bone metastasis on other modalities (Figure 2).
Bone-specific planar scintigraphy and SPECT tracer – 99mTc-MDP
Mechanism of action:
Increased uptake of radiotracers occurs in areas of osteoblastic reparative activity.
Pitfalls: (Figure 3)
- Reduced sensitivity to metastases isolated to the bone marrow as these are usually osteolytic.
- Flare response (increased radiotracer uptake that occurs early in the course of treatment) causes diagnostic confusion.
- Assessment of disease progression is limited to emergence of new lesions only. SPECT is not quantitative and therefore cannot assess the progression/regression of pre-existing lesions.
- Prolonged period (up to 6 months) is required for reduction of post-treatment bone activity.
PET tracers
PET has better spatial resolution compared to SPECT. PET tracers used in detection of skeletal metastasis can be bone-specific or non-specific tracers (Figure 4).
18F-Fluoride (18F-NaF)
18F-NaF is a bone-specific tracer. Uptake of 18F-NaF onto hydroxyapatite, the main inorganic component of bone, correlates with bone metabolism and vascularity (Figure 5).
Advantages of 18F-NaF: (Figure 6)
- Better pharmacokinetic characteristics.
- High quality images because of high bone to soft tissue activity ratio.
- Relatively short imaging time.
- Provides quantitative assessment of bone metabolism.
- Increased uptake in osteoblastic and mixed lesions that may not manifest as sclerosis on CT (Figure 7a-d).
Pitfalls of 18F-NaF: (Figure 8)
- High uptake in areas of elevated osteoblastic activity which can also be present in some benign processes.
- Detection of early bone marrow metastases is unclear.
- Small predominant lytic metastases are more likely to be missed (Figure 7e and 8).
- Flare phenomenon results in difficulty assessing treatment response at the early stage.
18F-Fluorodeoxyglucose (18F-FDG)
18F-FDG is a non-specific PET tracer and an analogue of glucose which is metabolised similarly to glucose. It targets tumour cells that are metabolically active (Figure 9).
Advantages of 18F-FDG:
- Detects both osseous and soft tissue metastases.
- It is a direct tumour-imaging agent as the tumours utilise the glucose-analogue molecules.
- In contrast to SPECT, it has high sensitivity for both lytic and marrow metastases.
- Useful in both restaging and assessment of treatment response.
Pitfalls of 18F-FDG:
- Limited use in detection of sclerotic metastases. Comparison of uptake in osteolytic and osteoblastic lesions is summarised in Figure 10.
- Diffuse uptake in marrow is seen after chemotherapy or granulocyte-colony stimulating factor, potentially causing false positive.
18F-Choline
18F-Choline tracers are being taken into cells by choline transporters, subsequently phosphorylated by choline kinase which is overexpressed in tumours, and finally the tracers are incorporated into cell membranes (Figure 11). The patterns of uptake and distribution are described in Figure 12.
Advantages of 18F-Choline: (Figure 13)
- It identifies skeletal, marrow-based and extra-skeletal disease (Figure 14).
- High sensitivity and specificity, eg. compared to bone scan.
- Useful in assessing treatment response and restaging.
Pitfalls of 18F-Choline:
- Sensitivity of the test is influenced by PSA levels; sensitivity increases with higher PSA levels.
- Sensitivity and therefore detection rate of microcarcinoma is limited by partial volume effect.
- Negative scans do not rule out metastasis.
- Inconsistent uptake in densely sclerotic bone lesions, especially after therapy.
- False positives in recent traumas and fractures.
68Ga-PSMA and 18F-PSMA
Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in all types of prostatic tissue, therefore it is a useful diagnostic and therapeutic target. 68Ga-PSMA and 18F-PSMA are conjugates of anti-PSMA monoclonal antibodies used in assessment of prostate malignancies (Figure 15).
Advantages of 68Ga-PSMA and 18F-PSMA:
- More superior than choline tracers in detecting prostate malignancy at low PSA levels.
- Detect both osseous and extra-osseous metastasis (Figure 16).
- Higher signal to noise ratio compared to 18F-Choline.
- Outperforms bone scan in detection of affected bone regions and assessment of overall bone disease volume.
- Higher sensitivity, specificity and overall accuracy in detecting skeletal metastases compared to whole body MRI.
Pitfalls of 68Ga-PSMA and 18F-PSMA:
- Limited detection of micrometastases resulting in false negatives.
- False positives in osteoarthritis, degenerative changes, fractures, Paget’s disease, haemangiomas, etc.
Current evidence
- 18F-NaF PET-CT is more superior to 99mTc-MDP planar scintigraphy and SPECT but comparable to DWI-MRI in the detection of bone metastases in prostate cancer patients. (Figure 17)
- No significant difference between radionuclide studies (SPECT-CT, 18F-NaF PET-CT, 18F-choline PET-CT) and whole-body-MRI in the detection of bone metastases in prostate cancer patients. (Figure 18)
- 68Ga-PSMA is more superior than whole-body-MRI in detecting bone metastases in prostate cancer. (Figure 19)
- Contrast-enhanced (CE)-PET-MR has higher sensitivity than CE-PET-CT in detecting osseous metastases in breast cancer patients. (Figure 20)