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Alpha v beta 3 integrin-targeting of intraperitoneally growing tumors with a radiolabeled RGD peptide.

Abstract：

:Ovarian cancer is the fourth most common cause of cancer deaths among females in the western world after cancer of the breast, colon and lung. The inability to control the disease within the peritoneal cavity is the major cause of treatment failure in patients with ovarian cancer. The majority of ovarian carcinomas express the alpha(v)beta(3) integrin. Here we studied the tumor targeting potential of an (111)In-labeled cyclic RGD peptide in athymic BALB/c mice with intraperitoneally (i.p.) growing NIH:OVCAR-3 human ovarian carcinoma tumors. The cyclic RGD peptide, c(RGDfK)E, was synthesized, conjugated with DOTA and radiolabeled with (111)In. The targeting potential of (111)In-DOTA-E-c(RGDfK) was studied in athymic mice with i.p. growing NIH:OVCAR-3 xenografts and the optimal dose of this compound was determined (0.01 microg up to 10 microg). The biodistribution at optimal peptide dose was determined at various time points (0.5 up to 72 hr). Furthermore, the therapeutic potential of (177)Lu-DOTA-E-c(RGDfK) was studied in this model. Two hours after i.p. administration, (111)In-DOTA-E-c(RGDfK) showed high and specific uptake in the i.p. growing tumors. Optimal uptake in the i.p. growing tumors was observed at a 0.03-0.1 microg dose range. Tumor uptake of (111)In-DOTA-E-c(RGDfK) peaked 4 hr p.i. [(38.8 +/- 2.7)% ID/g], gradually decreasing at later time points [(24.0 +/- 4.1)% ID/g at 48 hr p.i.]. Intraperitoneal growth of OVCAR-3 could be significantly delayed by injecting 37 MBq (177)Lu-labeled peptide i.p. Radiolabeled DOTA-E-c(RGDfK) is suitable for targeting of i.p. growing tumors and potentially can be used for peptide receptor radionuclide therapy of these tumors.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Dijkgraaf I,Kruijtzer JA,Frielink C,Corstens FH,Oyen WJ,Liskamp RM,Boerman OC

doi

10.1002/ijc.22297

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

605-10

issue

3

eissn

0020-7136

issn

1097-0215

journal_volume

120

pub_type

杂志文章

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