BACKGROUND: The aim of the study was to examine in vitro
and in vivo binding of radiolabelled analogues of P149 peptide
by experimental mammary adenocarcinoma with the intention
of potential application for diagnosis and internal radiotherapy
of tumours.
MATERIAL AND METHODS: The 36-amino acid peptide (P149-QY)
of 90% homology to 447–480 peptide fragment of hAFP was
synthesised and radiolabelled with iodine-125. The biodistribution
of P149-Q[125I]-Y was studied in experimental mammary
tumours. For in vitro experiments, extract from mouse mammary
tumours were prepared and incubated with radioiodinated
P149-QY peptide in the presence of a cross-linking reagent.
RESULTS: The gel electrophoresis analysis (SDS-PAGE)
showed that radioiodinated P149-QY peptide formed a complex
with adenocarcinoma proteins of about 30 kDa. The biodistribution
of P149-Q[125I]-Y studied in experimental mammary
tumours revealed a higher pharmacokinetic rate in comparison
with the whole radioiodinated AFP molecule. A moderate uptake
of P149-Q[125I]-Y in the tumour tissue was observed (3.2%
ID/g at 30-min p.i.v). However, a faster radioactivity clearance
from blood and normal tissues resulted in an increase in the
tumour/muscle (T/M) ratio, i.e. from 2.3 to 3.4 after 30 mins and
24 h p.i.v, respectively.
CONCLUSIONS: The present study shows that radioiodinated
P149-QY peptide reveals some positive features as the AFP
receptor radioligand, however, some additional structural modifications
of the initial peptide molecule are necessary for full
retention of the ligand-receptor interaction of its radiolabelled
forms
