title: Evaluation of bone-seeking novel radiotracer68Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast.
abstract: OBJECTIVE
  The successful labelling of bisphosphonates (BP) with68Ga using macrocyclic chelators such as the based triazacyclononane (NO2AP) is a step forward in the in-house availability of a novel bone-seeking PET radiopharmaceutical with dual advantage of PET/CT imaging and generator production. In this study, we compared the novel generator-based skeletal radiotracer68Ga-1,4,7-triazacyclonone-1,4-diacetic acid (68Ga-NO2AP-BP) with sodium fluoride (18F-NaF) for the detection of skeletal metastases in breast cancer patients. In addition, dosimetric analysis of68Ga-NO2AP-BP was performed in a subset of patients.
  
  
  METHODS
  This was a prospective study of histopathologically proven cases of breast cancer patients who were referred for bone scintigraphy and underwent positron emission tomography/computed tomography (PET/CT) with18F-NaF and68Ga-NO2AP-BP within a week in random order. The scans of each patient were compared both qualitatively for image quality and quantitatively for number of lesions and SUVmax of lesions. Dosimetric analysis was performed in five patients. Their PET/CT scans were acquired at multiple time points and urine and blood samples were collected. Dosimetric calculations were performed using OLINDA/EXM 1.1 software. Statistical analysis was done using Stata 13 (StataCorp) software package. An agreement analysis regarding number of lesions detected with the two skeletal radiotracers was carried out.
  
  
  RESULTS
  The image quality of68Ga-NO2AP-BP PET/CT scans were comparable to that of18F-NaF. There was no statistically significant difference in the SUVmax of lesions, normal bone and lesion to background ratio between the two skeletal radiotracers. There was good agreement in the number of lesions detected by both skeletal radiotracers. The mean whole body effective dose for68Ga-NO2AP-BP was 0.00583 mSv/MBq and the effective dose equivalent was 0.0086 mSv/MBq.
  
  
  CONCLUSIONS
  The excellent lesion detection agreement between68Ga-NO2AP-BP and18F-NaF favours the former as an alternative for skeletal scintigraphy in centres without an on-site cyclotron. The favourable dosimetric results and its potential to be used as a theranostic agent makes it an important generator-based skeletal radiotracer.
authors.affiliation: Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Averilicia
authors.initials: A
authors.lastname: Passah
authors.affiliation: Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Tripathi
authors.affiliation: Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Sanjana
authors.initials: S
authors.lastname: Ballal
authors.affiliation: Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Madhav Prasad
authors.initials: MP
authors.lastname: Yadav
authors.affiliation: Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Nuclear Chemistry, Johannes-Gutenberg-University, Mainz, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Roesch
authors.affiliation: Nuclear Chemistry, Johannes-Gutenberg-University, Mainz, Germany.
authors.forename: Marian
authors.initials: M
authors.lastname: Meckel
authors.affiliation: Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Partha
authors.initials: P
authors.lastname: Sarathi Chakraborty
authors.affiliation: Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India. csbal@hotmail.com.
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Bal
mesh_terms: D000328:Adult; D000368:Aged; D001372:Aza Compounds; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D002614:Chelating Agents; D004164:Diphosphonates; D005260:Female; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012969:Sodium Fluoride
chemical_list: D001372:Aza Compounds; D002614:Chelating Agents; D004164:Diphosphonates; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D010880:Piperidines; D019275:Radiopharmaceuticals; C482777:triazacyclononane; D012969:Sodium Fluoride
keywords: 18F-Sodium Fluoride; 68Ga-1,4,7-triazacyclonone-1,4-diacetic acid; Breast cancer; Positron emission tomography