Evaluation of 89Zr-Labeled Human Anti-CD147 Monoclonal Antibody as a Positron Emission Tomography Probe in a Mouse Model of Pancreatic Cancer

Abstract

IntroductionPancreatic cancer is an aggressive cancer and its prognosis remains poor. Therefore, additional effective therapy is required to augment and/or complement current therapy. CD147, high expression in pancreatic cancer, is involved in the metastatic process and is considered a good candidate for targeted therapy. CD147-specfic imaging could be useful for selection of appropriate patients. Therefore, we evaluated the potential of a fully human anti-CD147 monoclonal antibody 059-053 as a new positron emission tomography (PET) probe for pancreatic cancer.MethodsCD147 expression was evaluated in four pancreatic cancer cell lines (MIA Paca-2, PANC-1, BxPC-3, and AsPC-1) and a mouse cell line A4 as a negative control. Cell binding, competitive inhibition and internalization assays were conducted with 125I-, 67Ga-, or 89Zr-labeled 059-053. In vivo biodistribution of 125I- or 89Zr-labeled 059-053 was conducted in mice bearing MIA Paca-2 and A4 tumors. PET imaging with [89Zr]059-053 was conducted in subcutaneous and orthotopic tumor mouse models.ResultsAmong four pancreatic cancer cell lines, MIA Paca-2 cells showed the highest expression of CD147, while A4 cells had no expression. Immunohistochemical staining showed that MIA Paca-2 xenografts also highly expressed CD147 in vivo. Radiolabeled 059-053 specifically bound to MIA Paca-2 cells with high affinity, but not to A4. [89Zr]059-053 uptake in MIA Paca-2 tumors increased with time from 11.0±1.3% injected dose per gram (ID/g) at day 1 to 16.9±3.2% ID/g at day 6, while [125I]059-053 uptake was relatively low and decreased with time, suggesting that 059-053 was internalized into tumor cells in vivo and 125I was released from the cells. PET with [89Zr]059-053 clearly visualized subcutaneous and orthotopic tumors.Conclusion[89Zr]059-053 is a promising PET probe for imaging CD147 expression in pancreatic cancer and has the potential to select appropriate patients with CD147-expressing tumors who could gain benefit from anti-CD147 therapy.

Therapeutic efficacy evaluation of radioimmunotherapy with 90Y‐labeled anti‐podoplanin antibody NZ‐12 for mesothelioma

“…The absorbed doses of the other organs are also considered tolerable because these absorbed doses are lower than the tolerance doses of those organs based on the findings of external‐beam radiation studies . This is supported by several previous studies using 90 Y‐labeled antibodies, which showed no severe toxicities induced by similar absorbed doses . Therefore, the risk of radiation‐induced toxicity from RIT with 90 Y‐labeled NZ‐12 is expected to be low, although further dosimetry studies in malignant mesothelioma patients are required.…”

“…45,46 This is supported by several previous studies using 90 Y-labeled antibodies, which showed no severe toxicities induced by similar absorbed doses. 10,47 Therefore, the risk of radiation-induced toxicity from RIT with 90 Y-labeled NZ-12 is expected to be low, although further dosimetry studies in malignant mesothelioma patients are required. that the antitumor effect by RIT is limited, especially in radioresistant tumors, compared with external-beam radiation therapy as a result of lower radiation dose rates of RIT.…”

Glypican-3–Targeted 89Zr PET Imaging of Hepatocellular Carcinoma: Where Antibody Imaging Dares to Tread

“…However, the remarkable accumulation of 89 Zr-aGPC3 in HCC tumorsgreater than 800 %ID/g-overshadows liver uptake, yielding tumor-to-liver ratios greater than 30 in the larger (3.8-mm-diameter) tumor model. This ratio is substantially higher than that achieved with most other antibody probes, which have tumor-to-liver ratios ranging from 1.5 to 4 (10,16,(18)(19)(20) at their optimal time points after injection of 89 Zrlabeled antibody. These values are consistent with 89 Zr-aGPC3 uptake in smaller (,1-mmdiameter) tumors of the liver with a tumor-toliver ratio of 1.49-1.57 at 3-6 d after injection.…”

Immuno-PET Imaging of HER3 in a Model in which HER3 Signaling Plays a Critical Role

“…Mab#58, and the control antibody were conjugated with p -isothiocyanatobenzyl-desferrioxamine B (DF; Macrocyclics, Dallas, TX, USA) at DF at an antibody molar ratio of 3:1, as previously described [ 29 ]. The conjugation ratio of DF to antibody was estimated to be 2.3:1 to 2.5:1, as determined by size exclusion chromatography using a PD10 column (GE Healthcare, Buckinghamshire, UK) before purification.…”