Molecular Targeting
Technologies Radioactive and
Nonradioactive Probes
CONTROL ID: 1054031
TITLE: Positron emission tomography imaging of CD105 expression during tumor angiogenesis
AUTHORS/INSTITUTIONS: Y. Zhang, H. Hong, Y. Yang, J.W. Engle, T.E. Barnhart, R.J. Nickles, W. Cai, Radiology
and Medical Physics, University of Wisconsin - Madison, Madison, WI; B.R. Leigh, , TRACON Pharmaceuticals, Inc.,
San Diego, CA;
PRESENTER: Yin Zhang
AWARDS: Correlative Imaging Council Walter Wolf Young Investigator Award, Berson-Yalow Award , Young
Professional Committee (YPC) Award, MiCoE Young Investigator Award Symposium
CURRENT TRACK: Molecular Targeting Technologies - Radioactive and Nonradioactive Probes
CURRENT CATEGORY: Novel Radioactive Probes
ABSTRACT FINAL ID: 296;
ABSTRACT BODY:
Objectives : Overexpression of CD105 (endoglin) correlates with poor prognosis in many solid tumor types. Tumor
microvessel density (MVD) assessed by CD105 staining is the current gold standard for evaluating tumor
angiogenesis in the clinic. The goal of this study was to develop a positron emission tomography (PET) tracer for noninvasive imaging of CD105 expression.
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Methods : TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to DOTA and labeled with Cu.
FACS analysis and microscopy studies were performed to compare the CD105 binding affinity of TRC105 and DOTATRC105. PET imaging, biodistribution, blocking, and ex vivo histology studies were performed on 4T1 murine breast
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tumor-bearing mice to evaluate the ability of Cu-DOTA-TRC105 to target tumor angiogenesis. Another chimeric
antibody, cetuximab, was used as an isotype-matched control.
Results : FACS analysis of HUVECs revealed no difference in CD105 binding affinity between TRC105 and DOTA64
TRC105, which was further validated by fluorescence microscopy. Cu-labeling was achieved with high yield and
specific activity. Serial PET imaging revealed that the 4T1 tumor uptake of the tracer was 8.0 ± 0.5, 10.4 ± 2.8, and
9.7 ± 1.8 %ID/g at 4, 24, and 48 h post-injection respectively (n = 3), higher than most organs at late time points which
provided excellent tumor contrast. Biodistribution data as measured by gamma counting were consistent with the PET
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findings. Blocking experiments, control studies with Cu-DOTA-cetuximab, as well as ex vivo histology all confirmed
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the in vivo target specificity of Cu-DOTA-TRC105.
Conclusions : This is the first successful PET imaging study of CD105 expression. Fast, prominent, persistent, and
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CD105-specific uptake of Cu-DOTA-TRC105 in the 4T1 tumor was observed. Further studies are warranted and
currently underway.
SESSION TYPE: Oral
SESSION ABBREVIATION: 44
SESSION TITLE: Novel Radioactive Probes II: Tumor Probes - Part 1
SESSION ABSTRACT SORT ORDER: 5
Financial Disclosure 2011:
Yin Zhang: No financial interest/arrangement
Hao Hong: No financial interest/arrangement
Yunan Yang: No financial interest/arrangement
Jonathan Engle: No financial interest/arrangement
Todd Barnhart: No financial interest/arrangement
Robert Nickles: No financial interest/arrangement
Bryan Leigh: Yes, financial interest/arrangement ;TRACON Pharmaceuticals:Employee
Weibo Cai: No financial interest/arrangement
FDA Disclosure -Phy/Sci/Pharm (2): I do not have any applicable devices or drugs to disclose.
CONTROL ID: 1057817
TITLE: 18F FPPRGD2 in breast cancer subjects: A novel PET radiopharmaceutical for imaging αvβ3 integrin levels
AUTHORS/INSTITUTIONS: A. Iagaru, C. Mosci, E. Mittra, B. Shen, F.T. Chin, S.S. Gambhir, Radiology, Nuclear
Medicine, Stanford University Medical Center, Stanford, CA; X. Chen, Laboratory of Molecular Imaging and
Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD; M.L. Telli, Medical
Oncology, Stanford University Medical Center, Stanford, CA;
PRESENTER: Andrei Iagaru
AWARDS: Correlative Imaging Council Walter Wolf Young Investigator Award, Radiopharmaceutical Sciences Council
Young Investigator Award Symposium, Young Professional Committee (YPC) Award, MiCoE Young Investigator
Award Symposium
CURRENT TRACK: Molecular Targeting Technologies - Radioactive and Nonradioactive Probes
CURRENT CATEGORY: Probes for Oncology
ABSTRACT FINAL ID: 74;
ABSTRACT BODY:
Objectives : Angiogenesis is essential for tumor growth. The expression of αvβ3 on vascular endothelium has a key
role in this process. We have developed a novel PET radiopharmaceutical, 18F FPPRGD2 that is based on a dimeric
RGD peptide and targets the expression of αvβ3 integrins. We present data on the first breast cancer subjects imaged
with this tracer.
Methods : Six female subjects with breast cancer (average age: 54.7±9.8) were recruited. 18F FPPRGD2 and 18F
FDG PET/CT were subsequently performed within 2 weeks for each subject. The lesions detected with each test were
tabulated. Vital signs and EKGs were obtained at regular intervals. Blood samples were obtained before the injection
of 18F FPPRGD2, as well as at 24 hours and 1 week post-injection.
Results : 18F FPPRGD2 was tolerated without significant alterations in vitals, EKGs, or lab values. There was stable
distribution in all patients with primary clearance through the kidneys, as well as the liver, spleen, and bowel. When
the primary breast lesion was present (n=3), there was intense uptake of 18F FPPRGD2 at 45 minutes post-injection,
with SUVmax values ranging 8.1-9.4 (average: 8.75±0.9), compared to 18F FDG uptake with SUVmax value of 11.9.
Metastatic lesions (n=11) also showed intense uptake of 18F FPPRGD2, with SUVmax values ranging 4.8-9.4
(average: 7.12±1.9), compared to 18F FDG uptake with SUVmax values ranging 2.2-4.8 (average: 3.13±1.4).
Conclusions : 18F FPPRGD2 is a safe PET radiopharmaceutical, with desirable pharmacokinetic and biodistribution
characteristics for imaging αvβ3-integrin expression. Testing of 18F FPPRGD2 in subjects with breast cancer
demonstrates high uptake in the primary and in the metastatic lesions. Additional evaluation with larger cohorts is
required to confirm these preliminary findings.
Research Support : Stanford Cancer Center
SESSION TYPE: Oral
SESSION ABBREVIATION: 12
SESSION TITLE: Radiopharmaceutical Sciences Council Young Investigator Award Symposium
SESSION ABSTRACT SORT ORDER: 1
Financial Disclosure 2011:
Andrei Iagaru: No financial interest/arrangement
Camila Mosci: No financial interest/arrangement
Erik Mittra: No financial interest/arrangement
Bin Shen: No financial interest/arrangement
Frederick Chin: No financial interest/arrangement
Xiaoyuan Chen: No financial interest/arrangement
Melinda Telli: No financial interest/arrangement
Sanjiv Gambhir: No financial interest/arrangement
FDA Disclosure -Phy/Sci/Pharm (2): I do not have any applicable devices or drugs to disclose.