Time Evolution of DOTATOC Uptake in Neuroendocrine Tumors in View of a Possible Application of Radioguided Surgery with β- Decay.
A novel radioguided surgery (RGS) technique exploiting β- radiation has been proposed. To develop such a technique, a suitable radiotracer able to deliver a β- emitter to the tumor has to be identified. A first candidate is represented by 90Y-labeled DOTATOC, a compound commonly used today for peptide radioreceptor therapy. The application of this β- RGS to neuroendocrine tumors (NET) requires study of the uptake of DOTATOC and its time evolution both in tumors and in healthy organs and evaluation of the corresponding performance of the technique.


METHODS
Uptake by lesions and healthy organs (kidneys, spleen, liver and healthy muscle) was estimated on 177Lu-DOTATOC SPECT/CT scans of 15 patients affected by NET with different localizations, treated at IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. For each patient, SPECT/CT images, acquired at 0.5, 4, 20, 40, and 70 h after injection, were studied. For each lesion, the tumor-to-nontumor ratio (TNR) with respect to all healthy organs and its time evolution were studied. A subset of patients showing hepatic lesions was selected, and the TNR with respect to the nearby healthy tissue was calculated. By means of a Monte Carlo simulation of the probe for β- RGS, the activity that is to be administered for a successful detection was estimated lesion-by-lesion.


RESULTS
Uptake of DOTATOC on NETs maximized at about 24 h after injection. The cases of hepatic lesions showed a TNR with respect to the tumor margins compatible with the application of β- RGS. In particular, 0.1-mL residuals are expected to be detectable within 1 s with 5% false-negative and 1% false-positive by administering the patient as little as 1 MBq/kg.


CONCLUSIONS
The balance between tumor uptake and metabolic washout in healthy tissue causes the TNR to increase with time, reaching its maximum after 24 h, and this characteristic can be exploited when a radiotracer with a long half-life, such as 90Y, is used. In particular, if 90Y-DOTATOC is used with liver NET metastases, the proposed RGS technique is believed to be feasible by injecting an activity that is one third of that commonly used for PET imaging.
Dipartimento di Fisica, Sapienza Università di Roma, Roma, Italy INFN Sezione di Roma, Roma, Italy.
Francesco
F
Collamati
Dipartimento di Fisica, Sapienza Università di Roma, Roma, Italy INFN Sezione di Roma, Roma, Italy.
Fabio
F
Bellini
INFN Sezione di Roma, Roma, Italy.
Valerio
V
Bocci
Laboratori Nazionali di Frascati dell'INFN, Frascati, Italy.
Erika
E
De Lucia
Medical Physics Unit, IRCCS-ASMN, Reggio Emilia, Italy.
Valentina
V
Ferri
Medical Physics Unit, IRCCS-ASMN, Reggio Emilia, Italy.
Federica
F
Fioroni
Medical Physics Unit, IRCCS-ASMN, Reggio Emilia, Italy.
Elisa
E
Grassi
Medical Physics Unit, IRCCS-ASMN, Reggio Emilia, Italy.
Mauro
M
Iori
INFN Sezione di Roma, Roma, Italy Museo Storico della Fisica e Centro Studi e Ricerche "E. Fermi," Roma, Italy.
Michela
M
Marafini
INFN Sezione di Roma, Roma, Italy.
Silvio
S
Morganti
INFN Sezione di Roma, Roma, Italy.
Riccardo
R
Paramatti
INFN Sezione di Roma, Roma, Italy Museo Storico della Fisica e Centro Studi e Ricerche "E. Fermi," Roma, Italy Dipartimento di Scienze di Base e Applicate per l'Ingegneria, Sapienza Università di Roma, Roma, Italy.
Vincenzo
V
Patera
INFN Sezione di Roma, Roma, Italy.
Luigi
L
Recchia
Dipartimento di Fisica, Sapienza Università di Roma, Roma, Italy INFN Sezione di Roma, Roma, Italy Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Roma, Italy; and.
Andrea
A
Russomando
Laboratori Nazionali di Frascati dell'INFN, Frascati, Italy Dipartimento di Scienze di Base e Applicate per l'Ingegneria, Sapienza Università di Roma, Roma, Italy.
Alessio
A
Sarti
INFN Sezione di Roma, Roma, Italy Museo Storico della Fisica e Centro Studi e Ricerche "E. Fermi," Roma, Italy Dipartimento di Scienze di Base e Applicate per l'Ingegneria, Sapienza Università di Roma, Roma, Italy.
Adalberto
A
Sciubba
Dipartimento di Fisica, Sapienza Università di Roma, Roma, Italy INFN Sezione di Roma, Roma, Italy.
Martina
M
Senzacqua
Dipartimento di Fisica, Sapienza Università di Roma, Roma, Italy INFN Sezione di Roma, Roma, Italy.
Elena
E
Solfaroli Camillocci
Nuclear Medicine Unit, IRCCS-ASMN, Reggio Emilia, Italy.
Annibale
A
Versari
INFN Sezione di Roma, Roma, Italy.
Cecilia
C
Voena
Dipartimento di Fisica, Sapienza Università di Roma, Roma, Italy INFN Sezione di Roma, Roma, Italy riccardo.faccini@roma1.infn.it.
Riccardo
R
Faccini
D001610:Beta Particles; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging; D008099:Liver / Q000000981:diagnostic imaging; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000601:surgery*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D013154:Spleen / Q000000981:diagnostic imaging; D025321:Surgery, Computer-Assisted / Q000379:methods*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
C504257:177Lu-octreotide, DOTA(0)-Tyr(3)-; D019275:Radiopharmaceuticals; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide
DOTATOC uptake; neuroendocrine tumors; radioguided surgery; β− radiation