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. 2024 May 1;49(5):419-426.
doi: 10.1097/RLU.0000000000005139. Epub 2024 Mar 22.

Increasing Catecholamine Secretion Through NPY in Pheochromocytomas With False-Negative 123 I-MIBG Scintigraphy

Increasing Catecholamine Secretion Through NPY in Pheochromocytomas With False-Negative 123 I-MIBG Scintigraphy

Yutaro Ruike et al. Clin Nucl Med. .

Abstract

Introduction: 123 I-MIBG has been well established as a functional imaging tool, and 131 I-MIBG therapy is being considered for catecholamine-secreting tumors. Tumors with the characteristics of a noradrenergic biochemical phenotype, small, malignant, metastatic, extra-adrenal, bilateral, and hereditary, especially SDHx -related tumors, are reported to correlate with reduced MIBG uptake. However, the potential molecular mechanisms influencing MIBG uptake have been poorly studied.

Patients and methods: To identify critical genes that may enhance MIBG accumulation in pheochromocytomas (PCCs), we performed RNA-seq analyses for 16 operated patients with PCCs (6 MIBG-negative and 10 MIBG-positive) combined with RT-qPCR for 27 PCCs (5 MIBG-negative and 22 MIBG-positive) and examined primary cultures of the surgical tissues.

Results: In the present study, 6 adrenal nodules of 66 nodules surgically removed from 63 patients with PCCs (9%) were MIBG negative. MIBG, a guanethidine analog of norepinephrine, can enter chromaffin cells through active uptake via the cellular membrane, be deposited in chromaffin granules, and be released via Ca 2+ -triggered exocytosis from adrenal chromaffin cells. When we compared expression of several catecholamine biosynthesis and secretion-associated genes between MIBG-negative and MIBG-positive tumors using transcriptome analyses, we found that neuropeptide Y, which is contained in chromaffin granules, was significantly increased in MIBG-negative tumors. NPY stimulated norepinephrine secretion dose-dependently in primary cell culture derived from MIBG-positive PCC. In our study, MIBG-negative PCCs were all norepinephrine-hypersecreting tumors.

Conclusions: These data indicate that NPY upregulation in PCCs may stimulate chromaffin granule catecholamine secretion, which is associated with false-negative 123 I-MIBG scintigraphy.

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Conflict of interest statement

Conflicts of interest and sources of funding: The authors have declared no conflicts of interest. This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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