Synthesis and biological evaluation of RGD peptides with the 99mTc/188Re chelated iminodiacetate core: Highly enhanced uptake and excretion kinetics of theranostics against tumor angiogenesis

Byung Chul Lee, Byung Seok Moon, Ji Sun Kim, Jae Ho Jung, Hyun Soo Park, John A. Katzenellenbogen, Sang Eun Kim

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)782-792
Number of pages11
JournalRSC Advances
Volume3
Issue number3
DOIs
StatePublished - Jan 21 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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