PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA-knottin peptide

Research output: Contribution to journalJournal articleResearchpeer-review

Carsten Haagen Nielsen, Richard H Kimura, Nadia Withofs, Phuoc T Tran, Zheng Miao, Jennifer R Cochran, Zhen Cheng, Dean Felsher, Andreas Kjær, Juergen K Willmann, Sanjiv S Gambhir

Due to the high mortality of lung cancer, there is a critical need to develop diagnostic procedures enabling early detection of the disease while at a curable stage. Targeted molecular imaging builds on the positive attributes of positron emission tomography/computed tomography (PET/CT) to allow for a noninvasive detection and characterization of smaller lung nodules, thus increasing the chances of positive treatment outcome. In this study, we investigate the ability to characterize lung tumors that spontaneously arise in a transgenic mouse model. The tumors are first identified with small animal CT followed by characterization with the use of small animal PET with a novel 64Cu-1,4,7,10-tetra-azacylododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-knottin peptide that targets integrins upregulated during angiogenesis on the tumor associated neovasculature. The imaging results obtained with the knottin peptide are compared with standard 18F-fluorodeoxyglucose (FDG) PET small animal imaging. Lung nodules as small as 3 mm in diameter were successfully identified in the transgenic mice by small animal CT, and both 64Cu-DOTA-knottin 2.5F and FDG were able to differentiate lung nodules from the surrounding tissues. Uptake and retention of the 64Cu-DOTA-knottin 2.5F tracer in the lung tumors combined with a low background in the thorax resulted in a statistically higher tumor to background (normal lung) ratio compared with FDG (6.01±0.61 versus 4.36±0.68; P
Original languageEnglish
JournalCancer Research
Volume70
Issue number22
Pages (from-to)9022-30
Number of pages9
DOIs
Publication statusPublished - 2010

    Research areas

  • Animals, Antigens, CD31, Copper Radioisotopes, Cystine-Knot Miniproteins, Fluorescent Antibody Technique, Integrins, Mice, Mice, Transgenic, Mutation, Neoplasms, Neovascularization, Pathologic, Positron-Emission Tomography, Proto-Oncogene Proteins c-myc, Proto-Oncogene Proteins p21(ras), Radiopharmaceuticals, Sensitivity and Specificity, Tissue Distribution, Tomography, X-Ray Computed

ID: 32982663