Toward Radioguided Surgery with β⁻ Decays: Uptake of a Somatostatin Analogue, DOTATOC, in Meningioma and High-Grade Glioma

Abstract

A novel radioguided surgery (RGS) technique for cerebral tumors using β − radiation is being developed. Checking for a radiotracer that can deliver a β − emitter to the tumor is a fundamental step in the deployment of such a technique. This paper reports a study of the uptake of 90 Y-DOTATOC in meningiomas and high-grade gliomas (HGGs) and a feasibility study of the RGS technique in these types of tumor. Estimates were performed assuming the use of a β − probe under development with a sensitive area 2.55 mm in radius to detect 0.1-mL residuals. Methods: Uptake and background from healthy tissues were estimated on 68 Ga-DOTATOC PET scans of 11 meningioma patients and 12 HGG patients. A dedicated statistical analysis of the DICOM images was developed and validated. The feasibility study was performed using full simulation of emission and detection of the radiation, accounting for the measured uptake and background rate. Results: All meningioma patients but one with an atypical extracranial tumor showed high uptake of DOTATOC. In terms of feasibility of the RGS technique, we estimated that by administering a 3 MBq/kg activity of radiotracer, the time needed to detect a 0.1-mL remnant with 5% false-negative and 1% falsepositive rates is less than 1 s. Actually, to achieve a detection time of 1 s the required activities to administer were as low as 0.2-0.5 MBq/kg in many patients. In HGGs, the uptake was lower than in meningiomas, but the tumor-to-nontumor ratio was higher than 4, which implies that the tracer can still be effective for RGS. It was estimated that by administering 3 mBq/kg of radiotracer, the time needed to detect a 0.1-mL remnant is less than 6 s, with the exception of the only oligodendroma in the sample. Conclusion: Uptake of 90 Y-DOTATOC in meningiomas was high in all studied patients. Uptake in HGGs was significantly worse than in meningiomas but was still acceptable for RGS, particularly if further research and development are done to improve the performance of the β − probe. Radi oguided surgery (RGS) helps the surgeon evaluate the completeness of a tumor resection while minimizing the amount of healthy tissue removed (1). The surgeon is provided with vital and real-time information on the location and extent of the lesion and can assess the resection margins. The technique uses a radiolabeled tracer preferentially taken up by the tumor to discriminate cancerous tissue from healthy organs, as well as a probe (2) sensitive to the emission released by the tracer to identify in real time the targeted tumor focus. The radiopharmaceutical is administered to the patient before surgery.Current clinical applications of RGS are radioimmunoguided surgery for colon cancer (3,4), complete sentinel-node mapping for malignant melanoma (5) and breast cancer (6,7), and detection of parathyroid adenoma (8) and bone tumors (such as osteoid osteoma). There are also clinical studies on applications in neuroendocrine tumors (9,10).Established methods use a combination of a g-emitting tracer with a g-radiation-detec...

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].…”

“…Although on meningioma there could be larger SUVs (reaching also values > 6, see Ref. [9]), the uptake was rated sufficient to test the technique, in particular in an ex-vivo (i.e. background free) environment.…”

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

“…Previous studies have demonstrated the applicability of such a technique exploiting 90 Y-labeled peptides as a radiotracer in cases of meningioma and high-grade glioma (6). This paper represents the extension of those studies to NETs.…”

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

“…Heute et al used 68 Ga-DOTATOC to allow a pre-therapeutic assessment of patients with high grade glioma (HGG) undergoing a treatment with 90 Y-DOTATOC [73]. In a population including 11 patients with meningioma and 12 with HGG, Collamati et al [16] evaluated a possible approach to RGS with b -emitters. As concerning meningioma, all patients, but one with an atypical extracranial tumor, showed high uptake of 68 Ga-DOTATOC, with a TBR greater than 10 in almost all cases and usually above 20.…”

“…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].…”