Neuroendocrine tumors (NET) are the rare
tumors which often impose graveyard threat. These
tumors are characterized by the over expression of various
G-protein coupled receptors including
cholecystokinin (CCK) receptors-1 and 2 (A or B).
Minigastrin peptides are being investigated for
theranostic purposes of CCK-2 receptor positive NET. The
minigastrin analogue (APHO70) was modified by engineering
enzyme susceptible tetrapeptide sequence into APHO70
peptide to reduce the random degradation by lysosome
enzymes which pave the way to random trafficking in patient's body and
dipeptide addition at c-terminus. All the four modified
minigastrin peptides (MG-CL1-4) were investigated for lysosome
cathepsin B (catB)
enzyme susceptibility and fate into AR42J
cancer cell line. The
indium-111 labeled MG-CL1-4
peptides were also studied for target (
tumor) and non-target saccumulation by using
tumor induced mice. The RP-HPLC analysis result showed nonspecific cleavage of standard 111In-APH070 and 111In-MGCL1 while specific cleavage was noted in case of 111In-MGCL (2-4). The effect of specific and non-specific cleavage on biodistribution in
tumor induced nude mice model indicates the promising accumulation of 111In-MGCL2, 111In-MGCL3, and 111In-MGCL4 radiotracers while 111In-MGCL1 showed less accumulation. 111In-MGCL2 and 111In-MGCL3 showed highest target-to-kidney ratio (T/K) i.e. 1.71 and 1.72, respectively whereas standard compound showed T/K 1.13. In conclusion, the two
indium-111 labeled analogues i.e. 111In-MGCL2 and 111In-MGCL3 showed promising sensitivity for
tumor andcould be tested for further investigation to reach pre-clinical studies.