Synthesis and biological evaluation of 177Lu-DOTA-porphyrin conjugate: a potential agent for targeted tumor radiotherapy detection.
A novel unsymmetrically substituted water soluble porphyrin derivative namely, 5-(p-amino-propylene--oxyphenyl)-10,15,20-tris-(p-carboxy-methyl-ene-oxyphenyl)porphyrin was synthesized and coupled with a bifunctional chelating agent, viz. p-NCS-benzyl-DOTA (p-isothiocyanatobenzyl-1,4,7,10-tetra-aza-cyclodo-decane-1,4,7,10-tetra-acetic acid) for developing a suitable conjugate for use in targeted tumor therapy. The porphyrin-p-NCS-benzyl-DOTA conjugate was radiolabeled with 177Lu in good radiolabeling yield. Biodistribution studies performed in Swiss mice bearing fibrosarcoma tumors revealed high tumor uptake (5.33±1.11% injected activity per gm of tumor) within 30 min post-injection. The complex exhibited favorable tumor to blood and tumor to muscle ratios at various post-administration time points. Fast clearance of the non-accumulated activity was observed mostly through the renal pathway. Scintigraphic imaging studies performed in Swiss mice bearing fibrosarcoma tumors also exhibited selective accumulation of activity in the tumor.
Radiopharmaceuticals Division Bhabha Atomic Research Centre, Mumbai India - sharmila@barc.gov.in.
M
M
Bhadwal
S
S
Mittal
T
T
Das
H D
HD
Sarma
S
S
Chakraborty
S
S
Banerjee
M R
MR
Pillai
D000818:Animals; D005240:Feasibility Studies; D005260:Female; D005354:Fibrosarcoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D008187:Lutetium / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009928:Organ Specificity; D011166:Porphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011868:Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011878:Radiotherapy / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D011166:Porphyrins; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium