Peptide receptor radionuclide therapy (PRRT) is an emerging approach for patients with unresectable or metastatic
tumors. Our previously optimized
RGD peptide (3PRGD2) has excellent targeting specificity for a variety of
integrin αvβ3/αvβ5-positive
tumors and has been labeled with the therapeutic
radionuclide [177Lu]LuCl3 for
targeted radiotherapy of
tumors. However, the rapid clearance of [177Lu]Lu-
DOTA-3PRGD2 (177Lu-3PRGD2) in vivo requires two doses of 111 MBq/3 mCi to achieve effective
tumor suppression, limiting its further clinical application.
Albumin binders have been attached to drugs to facilitate binding to
albumin in vivo to prolong the
drug half-life in plasma and obtain long-term effects. In this study, we modified 3PRGD2 with
albumin-binding
palmitic acid (Palm-3PRGD2) and then radiolabeled Palm-3PRGD2 with 177Lu. [177Lu]Lu-
DOTA-Palm-3PRGD2 (177Lu-Palm-3PRGD2) retained a specific binding affinity for
integrin αvβ3/αvβ5, with an IC50 value of 5.13 ± 1.16 nM. Compared with
177Lu-3PRGD2, the 177Lu-Palm-3PRGD2 circulation time in blood was more than 6 times longer (slow half-life: 73.42 min versus 11.81 min), and the
tumor uptake increased more than fivefold (21.34 ± 4.65 %IA/g and 4.11 ± 0.70 %IA/g at 12 h post-injection). Thus, the significant increase in
tumor uptake and
tumor retention resulted in enhanced efficacy of
targeted radiotherapy, and
tumor growth was completely inhibited by a single and relatively lowdose of 18.5 MBq/0.5 mCi. Thus, 177Lu-Palm-3PRGD2 shows great potential for clinical application.