Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice.
OBJECTIVE
The aim of this study was to analyze the effect therapeutic injections of (177)Lu-DOTA(0)-Tyr(3)]-octreotate (DOTATATE) had on the tumor uptake of a subsequent injection with (111)In-DOTATATE in GOT1-bearing nude mice.


METHODS
Nude mice, xenografted with the human midgut carcinoid, GOT1, were first intravenously injected with a curative (30 MBq) or a suboptimal (7.5 MBq) amount of (177)Lu-DOTATATE. At various intervals thereafter (4-13 days), a second injection with (111)In-DOTATATE (0.5 MBq) was given. One (1) day after the second injection, the animals were sacrificed, tumor tissues collected, the tumor (111)In and (177)Lu activity concentration determined, and tumor regression/cell density was recorded.


RESULTS
In animals given curative amounts, the uptake of (111)In was lower than in untreated animals. On the other hand, a second late injection (3-13 days) after suboptimal amounts resulted in a twofold higher tumor activity concentration versus untreated animals. When the uptake of the curative injection was corrected for tumor cell density, which decreased from 66% to 4% over 2 weeks, an enhanced uptake per tumor cell was observed. The curative and suboptimal amounts resulted in a different uptake and retention of (177)Lu in tumors. The suboptimal amount resulted in a constant activity concentration, while the curative amount resulted in an increased activity concentration over time.


CONCLUSIONS
Our results, as presented in this paper, describe how the second injection in a fractionation protocol will be affected by the first therapeutic amount. This new information might be useful in the optimization of radionuclide therapy.
Bernhardt
Peter
P
Department of Radiation Physics, Sahlgrenska University Hospital, Göteborg, Sweden. peter.bernhardt@radfys.gu.se
Oddstig
Jenny
J
Kölby
Lars
L
Nilsson
Ola
O
Ahlman
Håkan
H
Forssell-Aronsson
Eva
E
D000818:Animals; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008187:Lutetium / Q000032:analysis / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011868:Radioisotopes / Q000493:pharmacokinetics; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
C499964:111In-octreotate, DOTA(0)-Tyr(3)-Thr(8)-; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; D011868:Radioisotopes; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D015282:Octreotide