Labelling, control and radiopharmacological evaluation of 99mTc-adenosine 5'-diphosphate (99mTc-ADP) as tumour seeking agent.
A study of 99mTc-adenosine-5'-diphosphate (99mTc-ADP) as a radiopharmaceutical for tumour diagnosis is presented. Two different labelling methods, using SnCl2 in alkaline solution and Zn as reducing agents, were developed. Reduction with Sn(II) alkaline solution was the selected method because a lower concentration of ADP (0.5 mg/mL) could be used and a higher radiochemical yield was achieved. A labelled molecule with a radiochemical purity higher than 95%, in vitro stability of at least 6 hours and an over all negative charge was obtained Biodistribution studies carried out in normal mice and rats revealed rapid urinary excretion and no specific accumulation of activity in any other particular organ. This behaviour was similar to that reported for 99mTc-adenosine-5'-triphosphate (99mTc-ATP). Rapid blood clearance, that could be fitted to a bicompartimental model, was also verified. No evidence of in vivo instability was observed. Studies in mice and rats bearing spontaneous mammary adenocarcinomas were performed and the results were compared to those from the 99mTc-ATP studies. Although the tumour models used were not the same, the incorporation of both labelled compounds was very similar. Radioactivity uptake in the tumour and the tumour-to-blood ratio were not notably high. However, a significant increment was observed in the tumour-to-muscle ratio (1.0 +/- 0.2 at 30 minutes to 2.7 +/- 0.4 at 240 minutes). Whole-body autoradiography enabled tumour visualization. Further investigations, including scintigraphic imaging, must be carried to complete the clinical evaluation of 99mTc-ADP as a tumour seeking agent.
Catedra de Radioquimica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
A S
AS
León
A M
AM
Rey
E T
ET
Leon
E O
EO
Savio
C
C
Kremer
C J
CJ
Lacava
A N
AN
Nappa
R N
RN
Chiozzone
E D
ED
Campos
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D000255:Adenosine Triphosphate / Q000737:chemistry; D000468:Alkalies / Q000737:chemistry; D000818:Animals; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D010084:Oxidation-Reduction; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D017971:Tin Compounds / Q000737:chemistry; D014018:Tissue Distribution; D015032:Zinc / Q000737:chemistry
D000468:Alkalies; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D017971:Tin Compounds; C094944:technetium Tc 99m adenosine diphosphate; C040736:technetium Tc 99m adenosine triphosphate; C023599:stannous chloride; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D015032:Zinc