Home
Resources
Publications
In Vivo Distribution of Avidin-Conjugated MX35 and (211)At-labeled, Biotinylated poly-L-lysine for Pretargeted Intraperitoneal α-radioimmunotherapy

In Vivo Distribution of Avidin-Conjugated MX35 and (211)At-labeled, Biotinylated poly-L-lysine for Pretargeted Intraperitoneal α-radioimmunotherapy

Sofia Helena Linnea Frost, Tom Bäck, Nicolas Chouin, Holger Jensen, Ragnar Hultborn, Lars Jacobsson, Sture Lindegren

Cancer Biother Radiopharm. 2011 Dec;26(6):727-36.

PMID: 22087606

Abstract:

Purpose:
Avidin-coupled monoclonal antibody MX35 (avidin-MX35) and astatine-211-labeled, biotinylated, succinylated poly-l-lysine ((211)At-B-PL(suc)) were administered in mice to assess potential efficacy as an intraperitoneal (i.p.) therapy for microscopic tumors. We aimed to establish a timeline for pretargeted radioimmunotherapy using these substances, and estimate the maximum tolerable activity.
Methods:
(125)I-avidin-MX35 and (211)At-B-PL(suc) were administered i.p. in nude mice. Tissue distributions were studied at various time points and mean absorbed doses were estimated from organ uptake of (211)At-B-PL(suc). Studies of myelotoxicity were performed after administration of different activities of (211)At-B-PL(suc).
Results:
We observed low blood content of both (125)I-avidin-MX35 and (211)At-B-PL(suc), indicating fast clearance. After sodium perchlorate blocking, the highest (211)At uptake was found in kidneys. Red bone marrow (RBM) accumulated some (211)At activity. Mean absorbed doses of special interest were 2.3 Gy/MBq for kidneys, 0.4 Gy/MBq for blood, and 0.9 Gy/MBq for RBM. An absorbed dose of 0.9 Gy to the RBM was found to be safe. These values suggested that RBM would be the key dose-limiting organ in the proposed pretargeting scheme, and that blood data alone was not sufficient for predicting its absorbed dose.
Conclusions:
To attain a favorable distribution of activity and avoid major toxicities, at least 1.0 MBq of (211)At-B-PL(suc) can be administered 24 hours after an i.p. injection of avidin-MX35. These results provide a basis for future i.p. therapy studies in mice of microscopic ovarian cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS741220	Poly-L-lysine, succinylated			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: