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.

CONCLUSION:

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: Sarika Sharma, Baljinder Singh, Anil K Mishra, Deepti Rathod, Puja Panwar Hazari, Krishna Chuttani, Shalini Chopra, Paramvir Mangat Singh, M L Abrar, Bhagwant R Mittal, Gurpreet Singh
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 29 Issue 7 Pg. 283-8 (Sep 2014) ISSN: 1557-8852 [Electronic] United States
• PMID: 25203145 (Publication Type: Journal Article)

Chemical References

• Large Neutral Amino Acid-Transporter 1
• Radiopharmaceuticals
• Technetium
• Pentetic Acid
• Methionine
• Technetium Tc 99m Pentetate

Topics

• Adult
• Aged
• Aged, 80 and over
• Breast Neoplasms (diagnosis)
• Female
• Humans
• Large Neutral Amino Acid-Transporter 1 (metabolism)
• Methionine
• Middle Aged
• Pentetic Acid
• Radiochemistry (methods)
• Radionuclide Imaging (methods)
• Radiopharmaceuticals
• Technetium
• Technetium Tc 99m Pentetate
• Tomography, Emission-Computed, Single-Photon (methods)
• Young Adult