Melanoma affine Tc-99m complexes of N-(2-diethylaminoethyl)benzamides.


Melanoma affine Tc-99m complexes of N-(2-diethylaminoethyl)benzamides.

Eisenhut, M.; Mohammed, A.; Mier, W.; Friebe, M.; Haberkorn, U.

Objectives: In the past a series of I-123 labeled N-(dialkylaminoalkyl)benzamides have been successfully applied to image human melanoma metastases. This prompted the development of Tc-99m complexes which should mimic the biological characteristics of these benzamide derivates.
Methods: Four N-(2-diethylaminoethyl)benzamide derivatives have been synthesized comprising the following phenyl substituents for Tc-99m complexation: 4-(Bz-S-Ac-Gly-Gly-NH) 1, 3-(NH2)-4-(Bz-S-Ac-Gly-NH) 2, 3-(Bz-S-Ac-NH)-4-(Bz-S-Ac-NH) 3, and 4-HS 4. The Tc-99m complexes were obtained by treating ligands 1-3 at 100°C for 10 minutes with Tc-99m pertechnetate, tartaric acid and stannous chloride as a reducing agend. Complex 4 was formed accordingly in the presence of N-methyl-3-azapentan-1,5-dithiol at 50°C. Biodistribution time-course studies were performed using C57B1/6 mice with subcutaneous B16 murine melanoma.
Results: The highest melanoma uptake was obtained with complex 1(3.42 and 4.48 %ID/G at 1 and 6 hr pi, respectively). The melanoma affinity decreased in the order 1>>4>2>>3.The melanoma uptake corresponded proportional with the blood values. Thus bioavailability of the Tc-complexes in the blood seemed to control melanoma uptake. A similar dependency was observed with radioiodinated benzamides.
Conclusion: Among the compounds tested so far complex 1 proved to exhibit high melanoma affinity and deserves further investigations as a melanoma seeking radiopharmaceutical.

  • The Journal of Nuclear Medicine, 40 (1999) 120-121

Permalink: https://www.hzdr.de/publications/Publ-1815
Publ.-Id: 1815