Feasibility of Absolute Quantitation of Myocardial ^99mTc-DPD Uptake in Patients with Suspected Transthyretin Cardiac Amyloidosis

Objectives: Transthyretin cardiac amyloidosis (ATTR) is caused by the extracellular deposition of amyloid fibrils in the heart and results in diastolic dysfunction, conduction abnormalities and congestive heart failure. ATTR can be caused by an inherited mutation TTR gene or by deposition of a wild-type protein associated with ageing. Diagnosis of ATTR and exclusion of light chain amyloidosis (AL) are important for correct patient management. ^99mTc-labelled biphosphonates are sensitive and specific for ATTR. We have assessed the feasibility of absolute quantitation of myocardial ^99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) uptake in patients with suspected ATTR using a quantitative software (Q.Metrix, GE Healthcare).

Methods: This dual-center, international study included 85 patients (m=69, age68.7+10.1 yrs) with suspected ATTR referred for ^99mTc-DPD. Planar whole body (WB) and SPECT/CT of the chest were performed. SPECT/CT data were corrected for motion, attenuation, scatter and collimator blurring. SPECT/CT activity concentration quantitation was performed using Q.Metrix given the injection information and system sensitivity. Cardiac activity was derived over 40% of maximum cardiac uptake. Mean cardiac uptake (MBq/ml) and % Injected dose (%ID) were compared to visual assessment (Perugini score [PS], 0-3) and to semi-quantitative assessment of planar data (heart/WB ratio.( Heart/spine and Heart/soft tissue concentration ratios were also obtained from SPECT/CT quantitation.

Results: 17/85 patients (m=14, age76.6+6.8 yrs) had positive ^99mTc-DPD studies. Two patients had PS1, 9 had PS 2 and 6 had PS 3. The mean cardiac concentration in PS 1 was 0.012+0.002, significantly lower than 0.053+0.004 (p=0.00001) and 0.040+0.002 (p=0.0007) in PS 2 and 3, respectively. Mean %ID was 0.48+0.06 in PS 1 and 2.68+0.17 (p<0.00001) and 2.44+0.20 (p=0.0001) in PS 2 and 3, respectively, with no significant difference in %ID between PS 2 and 3. Mean heart/WB ratio was 4.28+0.52 in PS 1 vs 7.27+0.66 (p=0.003) and 5.61+0.86 (p=0.16) in PS 2 and 3, respectively. In PS 1 the mean heart/spine concentration ratio was 0.34 and the mean heart/soft tissue concentration ratio 3.3+0.3, significantly lower compared to PS 2 and 3 (2.1+0.2 (p<0.0001), 12.2+2.1 (p=0.003) and 2.2+0.3 (p=0.001), 8.8+1.5 (p=0.012) respectively.

Conclusion: Absolute SPECT quantitation of cardiac ^99mTc-DPD uptake is feasible using Q.Metrix. Initial findings suggest significantly lower cardiac concentration and significantly lower cardiac %ID in PS 1, but no significant differences in %ID between PS 2 and 3. Further assessment in larger patient cohorts is needed to determine the value of SPECT quantitation over visual assessment and planar quantitation in ATTR and its role in diagnosis and potentially follow up/treatment response assessment. Research Support: GE Healthcare