Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide, and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model.
OBJECTIVE
(177)Lu-DOTA-Tyr(3)-octreotate is a candidate radiopharmaceutical for the therapy of somatostatin receptor (sstr)-positive small cell lung cancer (SCLC). Scintigraphy of lung tumors is made with 2 alternative somatostatin analogs, (111)In-DTPA-octreotide or (99m)Tc-depreotide. The aim of this study was to compare the biodistribution of these 3 radiopharmaceuticals in SCLC xenografted to nude mice.


METHODS
Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were intravenously injected with 10 MBq (2.4 microg) (99m)Tc-depreotide and 2 MBq (0.5 microg) (111)In-DTPA-octreotide simultaneously. The activity concentration (%IA/g) was measured in tumor and normal tissue at 2, 4, and 24 hours postinjection (hpi). The results were compared with earlier published biodistribution data of 3 MBq (0.7 microg) (177)Lu-DOTA-Tyr(3)-octreotate in the same animal model.


RESULTS
The activity concentration of (111)In-DTPAoctreotide in tumor was higher than the activity concentration of (99m)Tc-depreotide at 2-24 hpi, p < 0.05. The highest tumor uptake at 24 hpi was, however, found for (177)Lu-DOTA-Tyr(3)-octreotate. The activity concentration of (99m)Tc-depreotide was significantly higher in the heart, lungs, liver, the salivary glands, spleen, and bone marrow than for (111)In-DTPA-octreotide at 2-24 hpi. Saturation of the somatostatin receptors may have influenced the uptake in tumor and sstr-positive normal tissues.


CONCLUSIONS
The low tumor-to-lung and tumor-to-liver activity concentration ratios for (99m)Tc-depreotide could result in a lower detection rate of SCLC with this compound versus (111)In-DTPA-octreotide. (177)Lu-DOTA-Tyr(3)-octreotate gave the highest tumor-activity concentration, and has, thus, the best properties for therapy.
Schmitt
Anneli
A
Department of Radiation Physics, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. anneli.schmitt@radfys.gu.se
Bernhardt
Peter
P
Nilsson
Ola
O
Ahlman
Håkan
H
Kölby
Lars
L
Forssell-Aronsson
Eva
E
D000818:Animals; D018288:Carcinoma, Small Cell / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution
C497824:111In-octreotide, DTPA(0)-; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013004:Somatostatin; D004369:Pentetic Acid; C444119:technetium Tc 99m depreotide; C447941:lutetium Lu 177 dotatate; D015282:Octreotide