First-in-Human Total-Body PET/CT Imaging Using 89Zr-Labeled MUC5AC Antibody in a Patient with Pancreatic Adenocarcinoma

Harshad R. Kulkarni; Kevin A. Maupin; Tina Brennan; Jens Forsberg; Dan Rogers; Mark Olson; Brandon R. Mancini; Anthony Chang; Sreenivasa R. Chandana; Ryohei Kobayashi

doi:10.2967/jnumed.124.268074

We report on a 54-y-old man with stage pT3pN1pM1(HEP) pancreatic-head adenocarcinoma and liver metastasis. After diagnosis 20 mo previously, he underwent Whipple surgery and multiple chemotherapy regimens including folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin; gemcitabine/capecitabine; and gemcitabine/nab-paclitaxel. He recently underwent first-in-human imaging with ⁸⁹Zr-hNd2 (NMK89; Nihon Medi-Physics Co., Ltd.) for a phase 1 trial (NCT06129422) targeting mucin 5AC (MUC5AC)–positive pancreatic cancer. Of pancreatic adenocarcinomas, 64%–89% express MUC5AC, which is a secreted type of mucin and has a low normal-organ expression (1–3). In vitro studies of human pancreatic cancer tissue showed retention of MUC5AC around cancer cells and in the stroma (4). Therefore, radiolabeled antibodies binding to MUC5AC could potentially be used for molecular imaging and targeted radiomolecular therapy.

Biodistribution of the antibody at 1, 24, 72, and 168 h after injection was assessed using total-body PET/CT (Fig. 1). There were no adverse effects or lab changes up to 14 d after injection of ⁸⁹Zr-hNd2. Early results with ⁸⁹Zr-hNd2 suggest its potential in identifying candidates for MUC5AC-targeted treatments, including a theranostic approach with ²²⁵Ac, meriting continued investigation in clinical trials (4).

FIGURE 1.

Latest contrast-enhanced CT (A) revealed stable single liver metastasis (arrows), which was biopsied and stained positively for MUC5AC. Subsequent ⁸⁹Zr-hNd2 PET/CT series (B–E, maximum-intensity projections; F–I, axial PET/CT images) at 1, 24, 72, and 168 h after injection of 37 MBq of ⁸⁹Zr-hNd2 shows lesion SUV_max of 36.7 (24 h), 37.0 (72 h), and 35.3 (168 h), with increasing metastasis-to-liver SUV_max/SUV_mean ratios of 7.6, 14.2, and 27.2, respectively. Stable single liver metastasis was subsequently resected followed by stereotactic radiotherapy because of positive resection margin.

DISCLOSURE

This research was supported by AMED under grant JP17pc0101014. No other potential conflict of interest relevant to this article was reported.

Footnotes

Published online Sep. 5, 2024.

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