Gh. Hinkle et al., RADIOIODINATION, QUALITY ASSESSMENT, IN-VITRO AND IN-VIVO STABILITY OF I-125 NOFETUMOMAB, Journal of labelled compounds & radiopharmaceuticals, 41(5), 1998, pp. 423-434
Citations number
30
Categorie Soggetti
Chemistry Analytical","Chemistry Medicinal","Biochemical Research Methods","Pharmacology & Pharmacy
Iodine-125 radiolabeled monoclonal antibody (MAb) preparations used fo
r radioimmunoguided surgery should be prepared in a manner to insure a
stable, efficacious and safe product is used in clinical studies. A n
umber of MAbs have been radioiodinated and used for radioimmunoguided
surgery procedures including B72.3 and CC49. Individual MAbs and their
fragments differ in their physico-chemical response to conditions of
radiolabeling, effects of radiolysis, storage and general handling con
ditions. A radiolabeling and stability study was completed to evaluate
the radiochemical purity and immunoreactivity of NR-LU-10 Fab (nofetu
momab) radiolabeled with I-125 at three different specific activities
using the IODO-GEN(R) method. Ratios of 2:1, 1:1, 0.4:1 and 0.2:1(mCi/
mg) were used to determine the effects of increasing specific activity
on the in vitro stability in a range of potential patient dosages. Th
e radiochemical purity end immunoreactivity of each lot of radiolabele
d nofetumomab were determined on days 0, 8, 15, 22, 29 and 36 after ra
diolabeling using standard tests of instant thin layer chromatography
(ITLC), high performance liquid chromatography (HPLC) and whole cell b
inding assay of immunoreactivity. These standard tests indicated the r
adiochemical purity on the day of radioiodination was high for all spe
cific activity levels (98-99% for ITLC and >98% for HPLC). Preparation
s at ali specific activities showed a slight decrease in radiochemical
purity over time with the amount of unbound I-125 increasing or remai
ning unchanged. The immunoreactivity net bound showed excellent bindin
g with values ranging from 65-75%. The data indicate I-125 nofetumomab
undergoes in vitro physico-chemical changes over time. However, the c
hanges in radio-chemical purity and immunoreactivity were minimal and
should prove to be clinically insignificant.