Tc-99m-PEG-Liposomes for the Evaluation of Colitis in Crohn's Disease

Abstract

In the present study, the potential role of 99mTc-PEG-liposome to determine the extent and severity of active disease of Crohn's colitis was investigated. Patients suspected of having an exacerbation of Crohn's disease underwent a 99mTc-PEG-liposome scan (740 MBq, imaging at 4 and 24 h p.i.). A barium enema or endoscopy was performed as the standard verification procedure. Disease activity indices (Clinical Disease Activity Index and Van Hees Activity Index) were calculated. In seven patients positive images of colon segments affected by Crohn's colitis were obtained using 99mTc-PEG-liposomes. Only a moderate relation between 99mTc-liposome scan grading and verification procedures was found (Spearman rank r = 0.22). In accordance with previous studies, no significant correlation was found between the clinical disease activity indices and the verification procedures. This study was prematurely terminated because of unacceptable side-effects in 3 out of 9 patients, which occured almost immediately after starting the infusion. The complaints consisted of dyspnea and facial erythema. The symptoms were self-limiting when the infusion was stopped. In conclusion, the extent of Crohn's colitis can be established non-invasively with 99mTc-PEG-liposome scintigraphy. However, in view of the encountered side-effects, the PEG-liposomal preparation may have to be modified.

Hypersensitivity and Loss of Disease Site Targeting Caused by Antibody Responses to PEGylated Liposomes

“…Although PEGylated liposomes have not been reported to be immunogenic in humans, their iv administration is associated with hypersensitive infusion reactions in a substantial number of patients [43,44]. Unlike the reactions described here, these clinical events occur upon first exposure to the liposome and have been correlated with the activation of complement [45,46] and a rapid redistribution of the liposomes from the blood to the liver and spleen [43].…”

Complement activation-related pseudoallergy: A new class of drug-induced acute immune toxicity

“…To the authors' knowledge the first direct evidence for the causal relationship between C activation and HSRs to liposomes was provided by Brouwers et al (2000), who reported 3 severe HSRs out of 9 patients obtaining 99mTc-labeled pegylated liposomes for scintigraphic detection of bowel inflammation . In one reactor patient plasma C3, C4 and factor B decreased by 16-19%, implying major C consumption.…”

Formulation, characterization and tissue distribution of a novel pH-sensitive long-circulating liposome-based theranostic suitable for molecular imaging and drug delivery

“…a two-compartment elimination curve was used to model the blood activity over time for both formulas: 4%Peg-hs-chol, y=43. 36,37 have also been assessed and proven feasible for creating stable liposomes for SPECT imaging. We selected DTPA-derivatized phospholipid for our liposome formulation due to its known versatility in chelating metal of different imaging modalities.…”