Time Evolution of DOTATOC Uptake in Neuroendocrine Tumors in View of a Possible Application of Radioguided Surgery with β⁻ Decay

Abstract

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 90 Y-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 177 Lu-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-tonontumor 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. Conclusion: 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 halflife, such as 90 Y, is used. In particular, if 90 Y-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.

First ex vivo validation of a radioguided surgery technique withβ-radiation.

“…This is indeed the level of agreement of the predictions close to the skin and on the tumor bulk. This assessment strengthens the feasibility studies on meningioma, glioma and neuro-endocrine tumors already published [9,10].…”

Intraoperative β− detecting probe for radio-guided surgery in tumour resection

“…The study of the uptake of the radiotracer nearby the lesion showed that a tumor-non-tumor ratio (TNR) greater than 10 is observed in almost all the cases and a detailed simulation of the intraoperative probe allowed predictions of the RGS performance that resulted as very promising. Similar conclusions were recently achieved on neuro-endocrine tumors [7].…”

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

“…With respect to the specific type of detected radiation, they can be divided in g probes, the only ones widely diffuse in the surgical practice b -probes, and PET probes, detecting radiations originating from positron emitters [14][15][16][17][18].…”