Synthesis and evaluation of novel radioiodinated nicotinamides for malignant melanoma

• Published in: Nuclear medicine and biology 2008-10, Vol.35 (7), p.769-781
• Main Authors: Liu, Xiang, Pham, Tien Q, Berghofer, Paula, Chapman, Janette, Greguric, Ivan, Mitchell, Peter, Mattner, Filomena, Loc'h, Christian, Katsifis, Andrew
• Format: Article
• Language: English
• Subjects: A375 tumour; Animals; B16F0 tumour; Female; Iodine Radioisotopes; Iodine-123; Iodonicotinamides; Melanoma; Melanoma, Experimental - diagnostic imaging; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Niacinamide - metabolism; Radiology; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Small animal SPECT; Solubility; Tissue Distribution; Tomography, Emission-Computed, Single-Photon
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2008.05.011

Abstract Introduction A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N -2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. Methods [123 I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. Results The iodonicotinamides displayed low-affinity binding for σ1 –σ2 receptors ( Ki >300 nM). In biodistribution studies in mice, N -(2-(diethylamino)ethyl)-5-[123 I]iodonicotinamide ([123 I] 1 ) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h (∼8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N -alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [123 I] 1 , while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [123 I] 1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [123 I] 1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. Conclusion These findings suggest that [123 I] 1 , which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours.