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.

Keywords: [99m]Tc-methionine; breast scintimammography; cancer; single vial kit.

FIG. 1.

Whole body (anterior) images acquired at 0 minute, 10 minutes, 1 hour, and 2 hours following intravenous injection of 555.0 MBq of [99m]Tc-DTPA-bis-methionine showing normal biodistribution of the tracer. The arrows indicate the focal uptake of the radiotracer in the left breast lesion.

FIG. 2.

[99m]Tc-DTPA-bis-methionine-scintimammography images (acquired at 1, 2, and 4 hours) in a 66-year-old patient demonstrating increased tracer uptake in the left breast (positive lesion) as compared with the right breast (negative benign lesion, shown by arrows).

FIG. 3.

[99m]Tc-DTPA-bis-methionine-scintimammography images (acquired at 1, 2, and 4 hours) in a 25-year-old patient demonstrating bilateral normal breasts having no abnormal focal uptake of the radiotracer.