Pharmacokinetics of ^99mTc-MAA and ^99mTc-HSA-Microspheres used in pre-Radioembolization Dosimetry – Influence on the Liver-Lung Shunt

Abstract

Perfusion scintigraphy (PS) using technetium-99m (^99mTc) labeled albumin-aggregates is a mandatory step before hepatic radioembolization (RE) with yttrium-90-labeled microspheres. Within the bounds of a prospective clinical trial, this sub-analysis assessed the intrahepatic and intrapulmonary stability of two albumin-compounds, ^99mTc-MAA (macroaggregated serum albumin, MAA) and ^99mTc-HSA (human serum albumin, HSA) after intra-arterial injection. Methods: In n = 24 patients (age: 64.6y: 46.2-82.2) with metastatic colorectal cancer (mCRC), PS-data of both tracers were analyzed (n = 12 patients each). Biodistribution (liver, lung) and liver-lung shunt (LLS) was assessed by sequential planar scintigraphy (1h, 5h and 24h post intra-hepatic/intra-arterial injection; p.i.) using the region of interest (ROI) technique. Data were corrected for radioactive decay. Results: Liver uptake of MAA decreased significantly from 1h (median particle uptake=70.0%) to 5h (45.5%, p<0.0001) and 24h (27.9%, p<0.0001), respectively. MAA-uptake in the lungs at first increased significantly from 1h (2.7%) to 5h (3.8%, P = 0.0007) and then decreased significantly from 5h to 24h (3.0%, P = 0.002). HSA-uptake in the liver decreased significantly from 1h (70.2%) to 5h (65.0%, P = 0.0002) and from 1h to 24h (46.6%, p<0.0001). There was no significant change in pulmonary HSA-uptake (1h p.i: 2.4%) between time-points (p≥0.2). Liver-lung shunt (LLS) at 1h p.i. was 3.9% (25th/75th percentiles= 3.3/5.0%; range= 2.4-9.8%) for MAA and 3.2% (2.8/4.1%; 2.0-5.8%) for HSA (P = 0.2). MAA-LLS increased significantly from 1h (median LLS=3.9%) to 5h (7.7%, P = 0.0005) and 24h p.i. (9.9%, p<0.0001), respectively. HSA-LLS did not change significantly from 1h (3.2%) to 5h p.i. (3.5%, P = 0.74) but had increased significantly by 24h p.i. (4.8%, p>0.006). The estimated biologic half-lives of albumin particles were 7.9h/22.4h (bi-exponential fit, adj. R2 = 0.77) and 41.7h (mono-exponential fit, adj. R2 = 0.76) for MAA and HSA, respectively. Conclusion: In comparison to ^99mTc-MAA, ^99mTc-HSA-microspheres appear to be more resistant to degradation over time, allowing a reliable LLS-determination even at later time-points.