Synthesis and Application of Lactosylated, ^99mTc Chelating Albumin for Measurement of Liver Function

Abstract

Neogalactosylated and neolactosylated albumins are currently used as radiopharmaceutical agents for imaging the liver asialoglycoprotein receptors, which allows the quantification of hepatic liver function in various diseases and also in healthy liver transplant donors. We developed an original process for synthesizing a chelating neolactosylated human albumin using maleimidopropyl-lactose and maleimidopropyl-diethylene triamine pentaacetic acid (DTPA) derivatives. The lactosylated protein (LACTAL) conjugate showed excellent liver uptake compared to nonlactosylated protein and a very high signal-to-noise ratio, based on functional assessment of biodistribution in mice using (99m)Tc-scintigraphy.

Copolymer-Based Hepatocyte Asialoglycoprotein Receptor Targeting Agent for SPECT

“…About 0.185 MBq (in 100 mL of solution) of 99m Tc[P(VLA-co-VNI)](tricine) 2 (;1 · 10 29 mol of polymer/kg of body weight) was injected through the tail vein. At selected times (10,30, and 120 min), mice (n 5 5 at each time point) were sacrificed, and the tissues and organs of interest were collected, wet-weighed, and counted in a g-counter. The percentage injected dose per gram (%ID/g) for each sample was calculated by comparing its activity with an appropriate standard of ID.…”

“…99m Tc-GSA has been used clinically as an ASGP-R-binding radiopharmaceutical in Japan since 1992. The derivates of glycoprotein radiolabeled with 99m Tc (8)(9)(10)(11), 125 I/ 131 I (12), and 111 In (13) have been reported for SPECT applications. 68 Ga-deferoxamine-neogalactosylalbumin (14) and 18 F-fluorobenzoate galactosyl-neoglycoalbumin (15) were introduced as PET agents.…”

Towards In Vivo Imaging of Cancer Sialylation

“…Although glycans equip the cell surface with efficient and dynamic signalling mechanisms that have been partially deciphered to convey important clinical information, glycans and glycan-mediated interactions have been rarely targeted for in vivo imaging with some exceptions that particularly involve quantification of liver function [50–52]. …”

Development of single vial kits for preparation of 68Ga‐labelled hexavalent lactoside for PET imaging of asialoglycoprotein receptor

“…The 99m Tc‐labeled NGA was also developed by introducing 6‐hydrazinonicotinamide and dimercaptopropionyl groups as a bifunctional coupling agent. Due to the long synthesis steps and the instability of NGA, another ASGPR probe, the 99m Tc‐labeled LSA (neolactosyl HSA), was synthesized by simply conjugating commercially available lactose to HSA through reductive amination . Besides 99m Tc, glycosylated HSA was labeled for SPECT or PET imaging with various radioisotopes, including In‐111, I‐125/131, Ga‐67/68, and F‐18 .…”

“…Due to the long synthesis steps and the instability of NGA, another ASGPR probe, the 99m Tc-labeled LSA (neolactosyl HSA), was synthesized by simply conjugating commercially available lactose to HSA through reductive amination. [16][17][18] Besides 99m Tc, glycosylated HSA was labeled for SPECT or PET imaging with various radioisotopes, including In-111, 19,20 I-125/131, 21,22 Ga-67/68, [23][24][25][26] and F-18. 27 Although albumin-based ASGPR-targeted probes have been extensively evaluated, their application is limited by the regulations of biological products.…”