Abstract
To develop a companion set of RGD-based agents for diagnostic and radiotherapeutic purposes, facile incorporation of 99mTc(CO) 3 or 188Re(CO)3 into the same precursor produced, respectively, a structurally and functionally matched radiodiagnostic and radiotherapeutic - or theranostic - pair. This work presents the synthesis of two 99mTc-labeled RGD monomers (4 and 5) along with a 99mTc-labeled RGD dimer (6) and an investigation of the influence of the small-sized and negatively charged 99mTc-iminodiacetate (IDA) core on the in vitro and in vivo behavior of these three different RGD analogs for imaging integrin αvβ3 expression. Among the three 99mTc-IDA-RGD analogs, 6 exhibited the highest integrin binding affinity with an IC50 value of 0.5 nM and a tumor uptake with an ID/g value of 12.3 ± 5.15% at 60 min post-injection, whereas liver and intestinal levels remained relatively low with good metabolic stability (>97%), presumably because of the overall negative charge of the radiometal chelating system. Both 99mTc/188Re-labeled compounds (6 and 7), which were prepared from the precursor (18), provided a good tumor accumulation and a clearly visible image of the tumor with high contrast, as compared to the contralateral background in the U87-MG xenograft model. These data support the use of 99mTc- and 188Re-IDA-D-[c(RGDfK)] 2 as a matched radio-theragnostic pair that can be used to individualize radiotherapy for angiogenesis-dependent cancer.
Original language | English (US) |
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Pages (from-to) | 782-792 |
Number of pages | 11 |
Journal | RSC Advances |
Volume | 3 |
Issue number | 3 |
DOIs | |
State | Published - Jan 21 2013 |
ASJC Scopus subject areas
- Chemistry(all)
- Chemical Engineering(all)