68Ga-DOTA-D-Phe1-Tyr3-octreotide

PET with somatostatin receptor ligand [68Ga-DOTA-D-Phe1-Tyr3-octreotide ([68Ga]Ga-DOTA-TOC) is an established method in radiotherapy planning because of the improved detection and delineation of meningioma tissue.

Imaging of somatostatin receptors (SSTRs) using [111In]diethylenetriaminepentaacetic-acid-octreotide (DTPAOC) has proven to be helpful in the differentiation of meningiomas, neurinomas or neurofibromas, and metastases as well as in the follow-up of meningiomas ¹⁾.

A drawback of the SPECT method is its limited sensitivity in detecting small meningiomas. Because of PET's increased spatial resolution and its ability to absolutely quantify biodistribution, a PET tracer for SSTR imaging would be desirable.

[68Ga]DOTATOC seems to be a very promising new PET tracer for imaging SSTRs even in small meningiomas, offering excellent imaging properties and a very high tumor-to-background ratio.

(68)Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration. (68)Ga-DOTATOC-PET also allows detection of additional lesions in patients with multiple meningiomas ²⁾.

DOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery ³⁾.

Due to somatostatin receptor expression in meningiomas, PET with somatostatin analogues appears to be useful in radiotherapy treatment planning ⁴⁾.

The high uptake of (68)Ga-DOTA-TOC in meningiomas can be explained by the high values for vB and by the remarkably low values for k2 and k4, leading to significantly greater k1/k2 and k3/k4 ratios and RB in meningiomas than in reference tissue. Thus, pharmacokinetic modeling offers a more detailed analysis of biologic properties of meningiomas. In further studies, these data might serve as a basis for monitoring the somatostatin receptors of meningiomas after radiotherapy ⁵⁾.

Data demonstrate that [68Ga]-DOTATOC-PET improves target definition for FSRT in patients with intracranial meningiomas. Radiation targeting with fused DOTATOC-PET, CT, and MRI resulted in significant alterations in target definition in 73% ⁶⁾.

DOTATOC-PET/CT shows a high meningioma to background ratio which can be used to improve target volume definition prior to intensity modulated radiotherapy (IMRT). ⁷⁾ ⁸⁾.

Bashir et al. investigated the diagnostic accuracy of supplementary [68Ga]Ga-DOTA-TOC PET in patients with a 3-month postoperative MRI reporting gross-total resection (GTR).

Thirty-seven patients with a histologically proven meningioma and GTR on postoperative MRI were prospectively referred to [68Ga]Ga-DOTA-TOC PET. Detection and volume measurements of [68Ga]Ga-DOTA-TOC-avid lesions in relation to the primary tumor site were recorded. Residual tumor in suspicious lesions suggested by [68Ga]Ga-DOTA-TOC PET was verified by (i) tumor recurrence/progression on subsequent MRI scans according to the Response Assessment of Neuro-Oncology criteria, (ii) subsequent histology, and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scan.

Twenty-three PET scans demonstrated [68Ga]Ga-DOTA-TOC-avid lesions suspicious of residual meningioma, where 18 could be verified by (i) tumor progression on subsequent MRI scans (n = 6), (ii) histologic confirmation (n = 3), and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scans confirming the initial PET findings (n = 9) after an overall median follow-up time of 17 months (range, 9-35 months). In contrast, disease recurrence was seen in only 2 of 14 patients without [68Ga]Ga-DOTA-TOC-avid lesions (P < 0.0001). The sensitivity, specificity, and diagnostic accuracy of [68Ga]Ga-DOTA-TOC PET in detecting meningioma residue was 90% [95% confidence interval (CI), 67-99], 92% (95% CI, 62-100), and 90% (95% CI, 74-98; P < 0.0001), respectively.

The majority of patients with GTR on 3-month postoperative MRI may have small unrecognized meningioma residues that can be detected using [68Ga]Ga-DOTA-TOC PET ⁹⁾.

¹⁾

Nathoo N, Ugokwe K, Chang AS, Li L, Ross J, Suh JH, Vogelbaum MA, Barnett GH. The role of 111indium-octreotide brain scintigraphy in the diagnosis of cranial, dural-based meningiomas. J Neurooncol. 2007 Jan;81(2):167-74. Epub 2006 Jul 19. PubMed PMID: 16850106.

²⁾

Nyuyki F, Plotkin M, Graf R, Michel R, Steffen I, Denecke T, Geworski L, Fahdt D, Brenner W, Wurm R. Potential impact of (68)Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas. Eur J Nucl Med Mol Imaging. 2010 Feb;37(2):310-8. doi: 10.1007/s00259-009-1270-2. Epub 2009 Sep 18. PubMed PMID: 19763565.

³⁾

Gehler B, Paulsen F, Oksüz MO, Hauser TK, Eschmann SM, Bares R, Pfannenberg C, Bamberg M, Bartenstein P, Belka C, Ganswindt U. [68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning. Radiat Oncol. 2009 Nov 18;4:56. doi: 10.1186/1748-717X-4-56. PubMed PMID: 19922642; PubMed Central PMCID: PMC2785827.

⁴⁾

Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, Mäcke HR, Hofmann M, Debus J, Haberkorn U. PET imaging of somatostatin receptors using [68GA]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med. 2001 Jul;42(7):1053-6. PubMed PMID: 11438627

⁵⁾

Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher J, Strauss LG, Doll J, Mäcke HR, Eisenhut M, Debus J, Haberkorn U. Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas. J Nucl Med. 2005 May;46(5):763-9. PubMed PMID: 15872348.

⁶⁾

Milker-Zabel S, Zabel-du Bois A, Henze M, Huber P, Schulz-Ertner D, Hoess A, Haberkorn U, Debus J. Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOC-PET. Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):222-7. Epub 2006 Feb 20. PubMed PMID: 16488553.

⁷⁾

Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, Macke HR, Hofmann M, Debus J, Haberkorn U. PET imaging of somatostatin receptors using [68Ga]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med. 2001;42(7):1053–1056.

⁸⁾

Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher J, Strauss LG, Doll J, Macke HR, Eisenhut M, Debus J, Haberkorn U. Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas. J Nucl Med. 2005;46(5):763–769.

⁹⁾

Bashir A, Larsen VA, Ziebell M, Fugleholm K, Law I. Improved Detection of Postoperative Residual Meningioma with [68Ga]Ga-DOTA-TOC PET Imaging using a High-resolution Research Tomograph PET Scanner. Clin Cancer Res. 2021 Feb 1. doi: 10.1158/1078-0432.CCR-20-3362. Epub ahead of print. PMID: 33526423.