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[^99mTcOAADT]-(CH₂)₂-NEt₂: A Potential Small-Molecule Single-Photon Emission Computed Tomography Probe for Imaging Metastatic Melanoma

¹ Department of Radiology, Harvard Medical School, Boston, Massachusetts and ² Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts

Requests for reprints: Ashfaq Mahmood, Department of Radiology, Harvard Medical School, Armenise Building, 200 Longwood Avenue, Boston, MA 02115. Phone: 617-432-3995; Fax: 617-432-2419; E-mail: amahmood{at}hms.harvard.edu.

Evaluation of [^99mTc]oxotechnetium(V) complexes of the amine-amide-dithiol (AADT) chelates containing tertiary amine substituents as small-molecule probes for the diagnostic imaging of metastatic melanoma has shown that technetium-99m–labeled AADT-(CH₂)₂-NEt₂ (^99mTc-1) has the highest tumor uptake and other favorable biological properties. We have, therefore, assessed this agent in a more realistic metastatic melanoma model in which, after i.v. tail injection, a highly invasive melanoma cell line, B16F10, forms pulmonary tumor nodules in normal C57BL6 mice. Small melanotic lesions develop in the lungs and, on histologic examination, appear as small black melanoma colonies, increasing in size and number with time after tumor cell injection. Groups of mice received tumor cell inocula of 2 x 10⁵, 4 x 10⁵, or 8 x 10⁵ B16F10 cells; 14 days later, 2 hours after ^99mTc-1 administration, lung uptake of 2.83 ± 0.21%, 3.63 ± 1.07%, and 4.92 ± 1.61% injected dose per gram of tissue (% ID/g), respectively, was observed, compared with normal lung uptake of 2.13 ± 0.2% ID/g (P < 0.05). Additionally, a higher level of ^99mTc-1 accumulation was seen 17 days after tumor cell inoculation as the lung lesions grew. These in vivo studies coupled with additional in vitro and ex vivo assessment show that ^99mTc-1 has high and specific uptake in melanoma metastases in lungs and can potentially follow the temporal growth of these tumors.

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