Page 130 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Chapter 6
radiolabeled vectors on target-sites. Amongst these agents 4-(p-iodophenyl) butyric acid (I-PBA), previously discovered from a DNA-encoded chemical library [15, 16], has been used for such purposes. After coupling I-PBA with antibody fragments [17], folic acid radioconjugates [18, 19], DOTA-based bisphosphonates [20], and PSMA-directed radioligands [21] the desired effect of enhancing blood circulation was shown for the modified compounds. Hence, as a first effort to prolong the blood circulation time of [177Lu]Lu-DOTA- TATE to better match the half-life of 177Lu, we have selected I-PBA for coupling to DOTA-TATE. The above described studies have shown that conjugation of I-PBA and DOTA to a lysine is possible without abolishing the interaction of the molecule with albumin. Following this approach, we have incorporated I-PBA and a diglycolic spacer as depicted in Figure 1. We studied its binding capacity to the SSTR2 in vitro and its in vivo behavior in tumor-bearing mice, thereby also focusing on potential radiotoxicity in normal organs.
(a)
O
HO O
NN HO
NN O OH O
O HO
HO
OH
O
NH O
NH NH
O HN
NH
S S
NH
OHNO NH
NH
NH 2
OO HO
(b)
O
NN
O OH O NH
HO O
NN HO
OH
OO
NH NH NH NH O O NH NH
O O O O HN I HOO S
S
O OHNO
NH
NH 2
HO
HO
NH
NH
NH
OO HO
Figure 1 Chemical structure of (a) DOTA-Tyr3-octreotate; MW 1435 g/mol (b) Albutate-1; MW 2080 g/ mol, with in red the albumin binding domain.
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