RGDyC peptide-Modified PAMAM Dendrimer Conjugates Labeled with Radionuclide¹³¹I for SPECT Imaging and Radiotherapy of Lung Carcinoma

Objectives: Arginine-glycine-aspartic acid-tyrosine-cysteine(RGDyC)-modified PAMAM Dendrimer by polyethylene glycol-Poly(amidoamine) conjugates labeled with radionuclide ¹³¹I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer.

Methods: In this study, multifunctional generation five (G5) amine-terminated poly(amidoamine)(PAMAM) dendrimers were used as a platform to be sequentially conjugated with PEGylated arginine-glycine-aspartic acid-tyrosine-cysteine(RGDyC) peptide, followed by acetylation of the remaining dendrimer terminal amines. The formed dendrimer platform was labeled with radioactive iodine-131 (¹³¹I) to form the targeted theranostic dendrimeric nanoplatform ¹³¹I-RGDyC-PEG-PAMAM. Their targeting and therapeutic effects were subsequently evaluated in vitro and in vivo.

Results: We show that the PAMAM platform possessing approximately 33 PEG and 5.7 RGDyC moieties on each PAMAM. The dendrimer platform can specifically target human lung carcinoma A549 cells overexpressing αvβ3 integrin due to the attached RGD. With the attached Tyrosine moiety having the phenol group, the dendrimer platform can be effectively labeled with ¹³¹I with high radiochemical purity and good stability. Importantly, the ¹³¹I labeling renders the dendrimer platform with an ability to be used for targeted SPECT imaging and radiotherapy of an αvβ3 integrin-overexpressing lung carcinoma model in vivo.

Conclusions: The developed targeted theranostic dendrimeric nanoplatform ¹³¹I-RGDyC-PEG-PAMAM may hold promise to be used for targeted theranostics of human carcinoma.Keywords: PAMAM; RGD peptide; lung carcinoma; SPECT imaging; radiotherapy