N,N-(Dialkylamino)-alkyl substituted ^99mTc-amineamidedithiol (AADT) complexes as diagnostic probes for melanoma

In our effort to develop small molecular ^99mTc diagnostic probes to image malignant melanoma, tetradentate N₂S₂(AADT) ^99mTc-complexes of the general formula AADT-X-NR₂ (X = -(CH ₂) _n-, R = Et, Bu) were synthesized. The N-substituted AADT-X-NR₂ ligands were radiolabeled with ^99mTc(V) via transmetallation with [^99mTc]technetium(V)-glucoheptonate resulting in ^99mTc complexes in high radiochemical yield (86%-98%). These complexes were further characterized via HPLC coelution with similarly synthesized rhenium analogues. In-vitro evaluation in B16 murine melanoma cells revealed a distinct pattern of cell accumulation. The more lipophilic complex 2 [n = 2, R = Bu] displayed only an 8% melanoma uptake, whereas complex 1 [n = 2, R = Et] displayed a 44% cell uptake in 60 min. Complexes 3 [n = 3, R = Et] and 4 [n = 3, R = Bu] showed a 62% and 68% cell uptake at 60 min, respectively. In-vivo biodistribution studies in the C57B16/B16 mouse melanoma tumor model revealed a tumor accumulation of 7.6% ID/g at 60 min post injection (p.i.) and high melanoma/blood (10.8), melanoma/spleen (10.1) and melanoma/lung (7.3) ratios for complex 1. Although the tumor uptake of compound 3 was significantly lower (3.7% ID/g) at 60 min p.i., the melanoma/blood (19.1), melanoma/spleen (19.1) and melanoma /lung (12.7) ratios were considerably high. These results demonstrate the feasibility of developing N-substituted [^99mTc-AADT] complexes as small molecular probes for potential diagnostic imaging of malignant melanoma via SPECT.