99mTc-PYP SPECT/CT and 11C-PIB PET/CT for cardiac involvement of transthyretin and light-chain amyloidosis

Introduction: Cardiac amyloidosis (CA) is a rare form of restrictive cardiomyopathy caused by deposition of either misfolded transthyretin (ATTR) or light chain (AL). Electrocardiogram and echocardiography are initial screening tests but specificity is limited. Endomyocardial biopsy has high specificity but it is invasive and prone to sampling error. Scintigraphic evaluation with radiolabelled bisphosphonates, such as ^99mTc-pyrophosphate (^99mTc-PYP) and ¹¹C-PIB (amyloid-specific tracer) are proposed for evaluation of CA. Planar scintigraphy is known to be intrinsically obscured by overlapping bone uptake and cardiac blood pool activity, resulting in false positive diagnosis either by visual interpretation or quantification of myocardial-to-contralateral lung uptake ratio. This prospective study aims to evaluate the diagnostic utility of ^99mTc-PYP SPECT/CT and ¹¹C-PIB PET/CT for the detection of ATTR and AL CA, respectively.

Methods: Between year 2018 and 2021, a total of 45 patients (M: 35, F: 10; mean age=64.4 ± 13.1y) suspected of CA clinically and by echocardiography were referred for the same-day ^99mTc-PYP planar scintigraphy and SPECT/CT, and ¹¹C-PIB PET/CT. Cardiac planar scintigraphy and SPECT/CT were performed at 1 and 3h after IV administration of ^99mTc-PYP. Retention of ^99mTc-PYP was assessed visually (grade 0-3: where 0 = no uptake, 1 = uptake<rib, 2="uptake" equal="" rib="" to=""></rib,>3 = uptake>rib) and semi-quantitatively, using two identical circular regions of interest (ROIs) over the heart (H) and contralateral lung (CL), to estimate the <u>planar H/CL count</u><u>s ratio</u> on the anterior projection. We applied a widely recommended cut-off H/CL value >1.5 as positive diagnosis of ATTR CA. SPECT/CT was interpreted visually as positive for ATTR CA when ^99mTc-PYP uptake in the LV myocardium was greater than LV chamber blood-pool activity. The corresponding H/CL ratios were then semi-quantitatively calculated on the SPECT images (<u>SPECT H/CL count</u><u>s/pixel ratio</u>). Cardiac ¹¹C-PIB PET/CT was performed at 30 minutes post injection for qualitative assessment.

Results: Of 45 consecutive patients referred, 7/45 patients were confirmed as cardiac CA by standard consensus guidelines: 3/7 ATTR type and 4/7 AL type. By ^99mTc-PYP planar scintigraphic (PS) calculation, 12 patients were found to have 1-h PS H/CL value >1.5, thus 9/12 were considered false positive (FP) for ATTR CA by 1-h planar evaluation. However, 7 of these 9 FP patients had decreased H/CL value (<1.5) on 3-h planar imaging and only 2 remained high (H/CL value >1.5). Visual assessment of 1-h SPECT/CT correctly detected 3/45 ATTR CA by being able to definitively differentiate abnormal myocardial uptake from blood pool activity within the LV chamber. H/CL uptake ratio on 1-h SPECT/CT was significantly higher for ATTR CA than non-ATTR (7.45±0.94 vs. 2.88±0.58, p<0.01), which showed no significant change on 3-h SPECT/CT for both ATTR CA and non-ATTR (7.23±1.08 vs. 2.70±0.48), suggesting the lack of incremental value for a 3-h SPECT/CT. All 4 patients with AL CA were found on PET/CT to have significant ¹¹C-PIB uptake in LV myocardium to substantiate the presence of definite amyloid deposition while none of the ATTR type CA showed abnormal ¹¹C-PIB uptake.

Conclusions: Our results suggested that ^99mTc-PYP SPECT/CT performed at 1 hour post-injection could adequately detect ATTR cardiac amyloidosis, obviating the need to perform delayed imaging for minimizing blood pool activity. ¹¹C-PIB PET/CT has a good potential for non-invasive diagnosis of AL cardiac amyloidosis.