Improved detection of regional melanoma metastasis using 18F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide, a melanin-specific PET probe, by perilesional administration.

Abstract

UNLABELLED:

The efficacy of differing routes of administration of 18F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide (18F-MEL050), a new benzamide-based PET radiotracer for imaging regional lymph node metastasis in melanoma, was assessed.

METHODS:

B16-Black/6 metastatic melanoma cells harboring an mCherry transgene were implanted into the left-upper-foot surface of 49 C57 Black/6 mice as a model of popliteal lymph node (PLN) metastasis. Ultrasound scanning of the left PLN was performed at baseline and in combination with 18F-MEL050 PET on days 5, 9, and 14. Mice were divided into 2 groups to compare the results of tracer administration either subcutaneously at the tumor site (local) or in the lateral tail vein (systemic). After PET on each imaging day, 5 mice per group-including any with evidence of metastasis-were sacrificed for ex vivo validation studies including assessment of retained radioactivity and presence of the mCherry transgene as a surrogate of nodal tumor burden.

RESULTS:

Nine mice were judged as positive for PLN metastasis by ultrasound at day 5, and 8 PLNs were positive on 18F-MEL050 PET, 3 after systemic and 5 after local administration. Ex vivo analysis showed that ultrasound correctly identified 90% of positive PLNs, with 1 false-positive. 18F-MEL050 PET correctly identified 60% of positive PLNs after systemic administration and 100% after local administration with no false-positive results by either route. The average node-to-background ratio for positive PLNs was 6.8 in the systemic-administration group and correlated with disease burden. In the local-administration group, the mean uptake ratio was 48, without clear relation to metastatic burden. Additional sites of metastatic disease were also correctly identified by 18F-MEL050 PET.

CONCLUSION:

In addition to its potential for systemic staging, perilesional administration of 18F-MEL050 may allow sensitive and specific, noninvasive identification of regional lymph node metastasis in pigmented malignant melanomas.

• Authors: Delphine Denoyer, Titaina Potdevin, Peter Roselt, Oliver C Neels, Laura Kirby, Ivan Greguric, Andrew Katsifis, Donna S Dorow, Rodney J Hicks
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 52 Issue 1 Pg. 115-22 (Jan 2011) ISSN: 1535-5667 [Electronic] United States
• PMID: 21149487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorine Radioisotopes
• Melanins
• N-(2-(diethylamino)ethyl)-6-fluoronicotinamide
• Radiopharmaceuticals
• Niacinamide

Topics

• Animals
• Fluorine Radioisotopes
• Lymphatic Metastasis
• Melanins (metabolism)
• Melanoma (diagnostic imaging, secondary)
• Mice
• Mice, Inbred C57BL
• Niacinamide (analogs & derivatives)
• Polymerase Chain Reaction
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals
• Skin Neoplasms (diagnostic imaging, pathology)
• Ultrasonography