title: LAT-1 based primary breast cancer detection by [99m]Tc-labeled DTPA-bis-methionine scintimammography: first results using indigenously developed single vial kit preparation.
abstract: OBJECTIVE
  To evaluate the diagnostic utility of a single vial ready to label with [99m]Tc kit preparation of DTPA-bis-methionine (DTPA-bis-MET) for the detection of primary breast cancer.
  
  
  METHODS
  The conjugate (DTPA-bis-MET) was synthesized by covalently conjugating two molecules of methionine to DTPA and formulated as a single vial ready to label with [99m]Tc lyophilized kit preparations. Thirty female patients (mean age=47.5±11.8 years; range=21-69 years) with radiological/clinical evidence of having primary breast carcinoma were subjected to [99m]Tc-methionine scintigraphy. The whole body (anterior and posterior) imaging was performed on all the patients at 5 minutes, 10 minutes, 1 hour, 2 hours, and 4 hours following an intravenous administration of 555-740 MBq radioactivity of [99m]Tc-methionine. In addition, scintimammography (static images; 256×256 matrix) at 1, 2, and 4 hours was also performed on all the patients.
  
  
  RESULTS
  The resultant radiolabel, that is, [99m]Tc-DTPA-bis-MET, yielded high radiolabeling efficiency (>97.0%), radiochemical purity (166-296 MBq/μmol), and shelf life (>3 months). The radiotracer primarily gets excreted through the kidneys and localizes in the breast cancer lesions with high target-to-nontarget ratios. The mean±SD ratios on the scan-positive lesions acquired at 1, 2, and 4 hours postinjection were 3.6±0.48, 3.10±0.24, and 2.5±0.4, respectively. [99m]Tc-methionine scintimammography demonstrated an excellent sensitivity and positive predictive value of 96.0% each for the detection of primary breast cancer.
  
  
  CONCLUSIONS
  Ready to label single vial kit formulations of DTPA-bis-MET can be easily synthesized as in-house production and conveniently used for the scintigraphic detection of breast cancer and other methionine-dependent tumors expressing the L-type amino acid transporter-1 receptor. The imaging technique thus could be a potential substitute for the conventional single-photon emission computed tomography (SPECT)-based tumor imaging agents, especially for tracers with nonspecific mitochondrial uptake. However, the diagnostic efficacy of [99m]Tc-methionine needs to be evaluated in a large cohort of patients through further multicentric trials.
authors.affiliation: 1 Department of Nuclear Medicine & PET, PGIMER , Chandigarh, India .
authors.forename: Sarika
authors.initials: S
authors.lastname: Sharma
authors.forename: Baljinder
authors.initials: B
authors.lastname: Singh
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Deepti
authors.initials: D
authors.lastname: Rathod
authors.forename: Puja Panwar
authors.initials: PP
authors.lastname: Hazari
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Shalini
authors.initials: S
authors.lastname: Chopra
authors.forename: Paramvir Mangat
authors.initials: PM
authors.lastname: Singh
authors.forename: M L
authors.initials: ML
authors.lastname: Abrar
authors.forename: Bhagwant R
authors.initials: BR
authors.lastname: Mittal
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis*; D005260:Female; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism*; D008715:Methionine; D008875:Middle Aged; D004369:Pentetic Acid; D011854:Radiochemistry / Q000379:methods; D011877:Radionuclide Imaging / Q000379:methods*; D019275:Radiopharmaceuticals; D013667:Technetium; D016284:Technetium Tc 99m Pentetate; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D055815:Young Adult
chemical_list: D027283:Large Neutral Amino Acid-Transporter 1; D019275:Radiopharmaceuticals; D013667:Technetium; D004369:Pentetic Acid; D008715:Methionine; D016284:Technetium Tc 99m Pentetate
keywords: [99m]Tc-methionine; breast scintimammography; cancer; single vial kit