Does [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) soft tissue uptake allow the identification of patients with the diagnosis of cardiac transthyretin-related (ATTR) amyloidosis with higher risk for polyneuropathy?

Abstract

Background: With the introduction of several drugs for the therapy of transthyretin-related amyloidosis (ATTR) which slow down the disease, early detection of polyneuropathy (PNP) is becoming increasingly of interest. [99mTc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) bone scintigraphy, which is used for the diagnosis of cardiac (c)ATTR, can possibly make an important contribution in the identification of patients at risk for PNP.

Methods: Fifty patients with cATTR, who underwent both planar whole-body DPD scintigraphy and nerve conduction studies (NCS) were retrospectively evaluated. A subgroup of 22 patients also underwent quantitative SPECT/CT of the thorax from which Standardized Uptake Values (SUVpeak) in the subcutaneous fat tissue of the left axillar region were evaluated.

Results: The Perugini score was significantly increased in patients with cATTR and additional diagnosis of PNP compared to patients without (2.51 ± 0.51 vs 2.13 ± 0.52; P = 0.03). Quantitative SPECT/CT revealed that DPD uptake in the subcutaneous fat of the left axillar region was significantly increased in cATTR patients with compared to patients without (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04).

Conclusion: This study suggests that DPD bone scintigraphy is a useful tool for identification of patients with cATTR and a risk for PNP due to increased DPD soft tissue uptake.

Keywords: ATTR; Amyloidosis; Bone scintigraphy; Polyneuropathy.

Figure 1

Evaluation methodology of DPD bone scintigraphy for cardiac amyloidosis. (a) Showing the ROI localization for the skull uptake (red ROI1) as well as the ratio of soft tissue to humeral shaft (orange ROI 4 and pink ROI 7) and the soft tissue to femoral shaft estimation (blue ROI 8 and brown ROI 9) and (b) for the soft tissue tracer uptake of subcutaneous fat in the left axillar region

Figure 2

Diagram illustrating the division of patients discussed in the methods for further data analysis. This diagram illustrates the classification of patients discussed in methods for further data analysis

Figure 3

Comparison of the soft tissue tracer uptake of subcutaneous fat in the left axillar region in patients with vs without PNP using DPD SPECT/CT scintigraphy. (a) In the subgroup of the 22 patients with quantitative thoracic SPECT/CT the soft tissue tracer uptake of subcutaneous fat in the left axillar region was significantly increased in patients with PNP compared to patients without PNP (1.41 ± 0.58 vs 0.84 ± 0.58; P = 0.04). (b) After exclusion of patients with diabetes the soft tissue tracer uptake of subcutaneous fat in the left axillar region was still significantly increased in patients with PNP compared to patients without PNP (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04)

Figure 4

Representative examples for planar DPD bone scintigraphy of hATTR and wtATTR patients with and without PNP (with windowing of an upper threshold of 100% of the maximum). (a) a hATTR patient (his108arg) with PNP revealing a generally increased soft tissue uptake (Perugini score 3), (b) a wtATTR patient with PNP showing nearly absent bone uptake (Perugini score 3), (c) a hATTR patient (Val113Leu) without PNP with low-attenuated bone uptake (Perugini score 2), especially in the region of the femoral shaft, and (d) a wtATTR patient without PNP who also shows also only low-attenuated bone uptake (Perugini score 2)