Diagnostic versus therapeutic doses of [(177)Lu-DOTA-Tyr(3)]-octreotate: uptake and dosimetry in somatostatin receptor-positive tumors and normal organs.
OBJECTIVE
The aim of this study was to investigate the influence of a diagnostic versus therapeutic dose of [(177)Lu-DOTA-Tyr(3)]octreotate on the uptake, effects, and dosimetry in somatostatin receptor subtype 2(sst2)-positive tumors and normal organs in a rat tumor model.


METHODS
Lewis rats bearing rat pancreatic CA20948-tumor grafts were injected intravenously with different amounts of radioactivity and peptide of [(177)Lu-DOTA-Tyr(3)]octreotate: 3 MBq/0.5 microg (group A), 3 MBq/15 microg (group B), 300 MBq/15 microg (group C), and 555 MBq/15 microg (group D). Biodistribution studies were performed at several time points between 3 and 13 days post injection. Ex vivo and in vitro autoradiography was performed with frozen tumor sections.


RESULTS
Normal sst2-positive tissues showed a significantly higher uptake of radioactivity [%IA/g] when a low peptide amount was injected. On the other hand, the radioactivity concentration [%IA/g] in sst2-negative tissues and organs (blood, muscles, kidney, and liver) were comparable (groups A and B), independent of the injected peptide amount. Initially, this held true for the tumors as well. Yet, over time, we found a decrease in the radioactivity concentration in the tumors of groups A and B, because of tumor growth. On the other hand, therapeutic amounts of radioactivity (groups C and D) resulted in a significant reduction of tumor size, where radioactivity concentration remained higher than in groups A and B, despite the use of the high peptide amounts. Ex vivo autoradiograms of tumor sections confirmed these results. In vitro autoradiography performed on adjacent tumor sections revealed a reduced density of sst2 in tumors from animals that received a therapeutic radioactivity dose. Ki67-antibody immunohistochemistry showed an absence of proliferating tumor cells after therapy.


CONCLUSIONS
The differences in radioactivity retention in tumors after diagnostic or therapeutic doses, depending on a change in tumor kinetics, have to be taken into account when calculating tumor-absorbed radiation doses.
Müller
Cristina
C
Department of Nuclear Medicine, Erasmus MC Rotterdam, The Netherlands. c.muller@erasmusmc.nl
Forrer
Flavio
F
Bernard
Bert F
BF
Melis
Marleen
M
Konijnenberg
Mark
M
Krenning
Eric P
EP
de Jong
Marion
M
D000818:Animals; D001345:Autoradiography; D006262:Health; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011874:Radiometry; D051381:Rats; D011917:Rats, Inbred Lew; D017481:Receptors, Somatostatin / Q000378:metabolism*
D019394:Ki-67 Antigen; D009942:Organometallic Compounds; D017481:Receptors, Somatostatin; C447941:lutetium Lu 177 dotatate; D015282:Octreotide