^99mTc-Sestamibi Scintigraphy to Monitor the Long-Term Efficacy of Enzyme Replacement Therapy on Bone Marrow Infiltration in Patients with Gaucher Disease

Abstract

Assessing the skeletal response to enzyme replacement therapy (ERT) in Gaucher disease (GD) is problematic. We investigated the reliability of 99m Tc-sestamibi scintigraphy in monitoring changes in bone marrow involvement induced by ERT. Methods: In 52 GD patients, the efficacy of ERT on bone marrow disease was monitored using at least 2 sequential 99m Tc-sestamibi scans; 17 patients were receiving ERT at enrollment, and 35 were ERT-naïve. We elaborated a dose-response model by statistical analysis based on linear mixed models. Results: Patients whose marrow disease improved had received a significantly higher ERT dose per month than patients who did not improve. Significantly more patients reached near-disappearance of marrow disease if their disease burden at enrollment had been lower and the duration of clinical signs shorter. The response of the marrow scintigraphic score was more pronounced in ERT-naïve patients. No relevant effect of ERT on marrow disease was observed until platelet count and splenomegaly had improved. Conclusion: Although based on localized evaluation, changes in the 99m Tc-sestamibi score closely correlated with the main determinants of ERT, with a definite dose-response relationship. The threshold at which ERT induced any improvement in bone marrow disease was 35-36 U/kg/mo; in ERT-naïve patients, the scintigraphic score declined by 1 unit after ERT at 28 U/kg/mo.

Standardization of MRI and Scintigraphic Scores for Assessing the Severity of Bone Marrow Involvement in Adult Patients With Type 1 Gaucher Disease

“…Different techniques and different scoring systems to semiquantitatively assess the burden of bone marrow infiltration in GD have been described over the past 30 years using either MRI or scintigraphy [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Experience is also growing with MRI with quantitative chemical shift to measure the fat fraction of bone marrow in the vertebral bodies, which in adult patients with GD is inversely correlated with the degree of infiltration by Gaucher cells [41][42][43][44].…”

“…Two scintigraphic approaches among several previously proposed methods are available and feasible in any nuclear medicine department, namely bone marrow scintigraphy with 99m Tc-radiocolloid and scintigraphy with 99m Tc-sestamibi [33,37,45]. Although the former provides indirect assessment of bone marrow infiltration (as the radiocolloid accumulates in normally functioning, noninfiltrated bone marrow), the latter directly depicts areas of bone marrow infiltrated by Gaucher cells [40].…”

Differential Diagnosis of Rare Diseases Involving Bilateral Lower Extremities with Similar 99mTc-MDP Bone Scan Patterns: Analysis of a Case Series

“…Giuliano et al reported that 99m Tc-Sestamibi uptake reliably identified bone marrow infiltration by Gaucher's cells, and that scintigraphic score was highly correlated with the severity of bone marrow involvement. The series work by the authors together with others' indicated the feasibility of directly imaging bone marrow infiltration using 99m Tc-Sestamibi in the early phases of Gaucher's disease [6][7][8]. However, biodistribution of 99m Tc-Sestamibi did not seem to coincide with that of 99m Tc-MDP [9].…”

Imaging of non-neuronopathic Gaucher disease: recent advances in quantitative imaging and comprehensive assessment of disease involvement

“…Nuclear medicine studies are not routinely used for routine follow-up assessment of Gaucher disease at most institutions, although 99 m-Tc-Sestamibi scintigraphy has been studied as an alternative means of quantifying bone marrow involvement with good agreement with MRI-based semi-quantitative scoring [101, 102]. Treatment-related changes have been successfully observed using 99 m-Tc-Sestamibi scintigraphy [103]. Other scintigraphy methods are largely ineffective at quantifying marrow involvement as typical bone radiotracers are only taken up by normal marrow, but 99 m-Tc-MDP could potentially be helpful in discerning between bone crises and osteomyelitis, although this observation is not well validated [22].…”