title: An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the alpha v beta 3-selective angiogenesis imaging agent 99mTc-NC100692.
abstract: BACKGROUND
  The alpha(v)beta(3) integrin is one of the angiogenesis-related membrane proteins highly expressed on the neovasculature of breast cancer and lung carcinomas. Labeling of the alpha(v)beta(3) integrin with (99m)Tc-NC100692 provides a potential tool for imaging angiogenesis and hence the presence of malignant lesions.
  
  
  OBJECTIVE
  To determine the feasibility of detecting metastatic lesions in liver, lung, bone, and brain with scintigraphy using the alpha(v)beta(3)-avid imaging agent (99m)Tc-NC100692 in patients with breast or lung cancer, and to assess its safety profile.
  
  
  METHODS
  Twenty-five patients--15 with lung cancer and 10 with breast cancer--were recruited at 10 centers. Metastases were newly diagnosed by computed tomography, magnetic resonance imaging, or bone scintigraphy, i.e., the reference standard. Patients underwent whole-body scans of approximately 10-15 min duration beginning at 45 min post-injection and a SPECT acquisition of approximately 30 min beginning at 75 min after injection of up to 1100 MBq (99m)Tc-NC100692. In case of liver metastases, dynamic acquisitions of 15 min were performed starting immediately post-injection. Safety measurements were performed up to 2.5 hours after injection and included hematology, serum biochemistry, coagulation, urine analysis, vital signs, oximetry, 12-lead ECG assessments, and a physical examination.
  
  
  RESULTS
  In patients with breast cancer, (99m)Tc-NC100692 scintigraphy detected 1 of 7 liver, 4 of 5 lung, 8 of 17 bone, and 1 of 1 brain metastases. The corresponding numbers for lung cancer patients were 0 of 2, 17 of 18, 2 of 2, and 7 of 9. There was overall stability through the follow-up period for all investigated safety parameters.
  
  
  CONCLUSIONS
  Scintigraphy with (99m)Tc-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of (99m)Tc-NC100692 is safe and well tolerated.
authors.affiliation: Division of Radiology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. rimma.axelsson@ki.se
authors.forename: Rimma
authors.initials: R
authors.lastname: Axelsson
authors.forename: Tore
authors.initials: T
authors.lastname: Bach-Gansmo
authors.forename: Juan
authors.initials: J
authors.lastname: Castell-Conesa
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McParland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000473:pathology*; D003287:Contrast Media; D005060:Europe; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging*; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed; D014481:United States
chemical_list: D003287:Contrast Media; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C514230:technetium 99m NC 100692