68Ga-Pentixafor PET/CT highly-sensitive for diagnosis and staging of Grade 3 NETs and NECs

Liz Meszaros, MDLinx

North American Neuroendocrine Tumor Society (NANETS) 10th Annual Symposium

Philadelphia, Pennsylvania, United States | October 19-21, 2017


Philadelphia, PA, October 19, 2017—In patients with Grade 3 neuroendocrine tumors (NETs) or neuroendocrine carcinomas (NECs), 68Ga-Pentixafor may provide excellent diagnostic and staging information, and is a viable PET tracer shown to target chemokine receptor 4 (CXCR4) in tumor-bearing mice, according to results presented here at the North American Neuroendocrine Tumor Society (NANETS) 2017 Symposium.

Take-home messages

  • 68Ga-Pentixafor may provide excellent diagnostic and staging information iIn patients with Grade 3 neuroendocrine tumors (NETs) or neuroendocrine carcinomas (NECs.
  • 68Ga-Pentixafor is a viable PET tracer shown to target chemokine receptor 4 (CXCR4).

Although somatostatin receptor type 2 (SSTR2) directed peptide-receptor radiotherapy (PRRT) improves outcomes in patients with Grade 1 and Grade 2 NETs, those with Grade 3 NETs or NECs are not so lucky. Consequently, patients with Grade 3 NETs are desperately in need of new and improved diagnostic and staging modalities.

“Even though neuroendocrine tumors are slow, indolent, [they are] still aggressive and some can recur. Current treatment plans still focus on SSTR2. Somehow, with low grade (Grade 1 or 2), it is kind of effective, but moderate as the grade advances to high grade. So the response is partial or even poor for the high grade,” said lead author Dijie Liu, PhD, research assistant and scientist, University of Iowa, Iowa City, IO.

“We are thinking of targeting to some new receptors for treatment, especially for the metastatic recurrences,” she added.

Dr. Liu and colleagues conducted this study to determine the validity of their hypothesis that Pentixafor, a CXCR4 antagonist, will bind to CXCR with high specificity and affinity, and that 68Ga-Pentixafor PET/CT will be highly-sensitive for the diagnosis and staging of G3 NETs and NECs.

Using qGPCR array assay and flow cytometry, Dr. Liu and colleagues quantified somatostatin receptor type 2 (SSTR2) and CXCR4 gene expression in high-grade cell lines, including new cell line (SKS), uterine carcinoma and IMR32, and neuroblastoma.

In tumor-bearing mice, DOTATOC and Pentixafor were labeled with 203Pb- for SPECT/CT imaging and 68Ga- for PET/CT imaging.

High levels of SSTR2 and CXCR4 were expressed by IMR32, while SKS cells expressed a moderate levels of CCXCR4 and minimal SSTR2 both in vitro and in vivo. Dr. Liu and colleagues observed that 203PB-DOTATOC and 68Ga-DOTATOC targeted SSTR2-expressing tumor xenografts specifically.

Finally, they observed that PET/CT imaging using 68Ga-Pentixafor evidenced a high uptake in CXCR4-expressing tumors, at 5.8% ID/g, and primarily renal clearance with partial distribution to the digestive tract.

“We know that, especially for metastases and recurrence, it’s very important not only just to consider tumor cell overexpression, but also the microenvironment, that may include not only just the tumor cells but also the stromal cells, fibroblasts, and how the tumor cell responds,” said Dr. Liu.

“CXCR4 is kind of unique, and was once described as ‘ubiquitous’ because it has been reported to be overexpressed in over 30 types of tumors. So it’s worth investigating, and hopefully, with some preliminary pre-clinical data, it will provide more toxicity and also therapeutic efficacy studies for the future for clinical application,” she concluded.