RESISTing the Need to Quantify: Putting Qualitative FDG-PET/CT Tumor Response Assessment Criteria into Daily Practice

Peacock, Justin G.; Christensen, CW; Banks, Kevin

doi:10.3174/ajnr.a6294

Cited by 10 publications

(10 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Conventionally, therapy response monitoring relies on categorizing measurements of predefined changes in either tumor size (Eisenhauer et al 2009) or tumor FDG uptake by PET (Wahl et al 2009;Peacock et al 2019). However, given that tumor cell death is a desired endpoint of anticancer therapies, specific and robust in vivo measures are being intensively investigated preclinically and clinically (Smith and Smith 2012;Zhang et al 2019;Zhang et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMAB®

Liapis

Tieu

Rudd

et al. 2020

EJNMMI radiopharm. chem.

View full text Add to dashboard Cite

Purpose The chimeric monoclonal antibody (mAb) chDAB4 (APOMAB®) targets the Lupus associated (La)/Sjögren Syndrome-B (SSB) antigen, which is over-expressed in tumors but only becomes available for antibody binding in dead tumor cells. Hence, chDAB4 may be used as a novel theranostic tool to distinguish between responders and nonresponders early after chemotherapy. Here, we aimed to ascertain which positron emitter, Zirconium-89 ([89Zr]ZrIV) or Iodine-124 ([124I]I), was best suited to label chDAB4 for post-chemotherapy PET imaging of tumor-bearing mice and to determine which of two different bifunctional chelators provided optimal tumor imaging by PET using [89Zr]ZrIV-labeled chDAB4. Methods C57BL/6 J mice bearing subcutaneous syngeneic tumors of EL4 lymphoma were either untreated or given chemotherapy, then administered radiolabeled chDAB4 after 24 h with its biodistribution examined using PET and organ assay. We compared chDAB4 radiolabeled with [89Zr] ZrIV or [124I] I, or [89Zr]Zr-chDAB4 using either DFO-NCS or DFOSq as a chelator. Results After chemotherapy, [89Zr]Zr-chDAB4 showed higher and prolonged mean (± SD) tumor uptake of 29.5 ± 5.9 compared to 7.8 ± 1.2 for [124I] I -chDAB4. In contrast, antibody uptake in healthy tissues was not affected. Compared to DFO-NCS, DFOSq did not result in significant differences in tumor uptake of [89Zr]Zr-chDAB4 but did alter the tumor:liver ratio in treated mice 3 days after injection in favour of DFOSq (8.0 ± 1.1) compared to DFO-NCS (4.2 ± 0.7). Conclusion ImmunoPET using chDAB4 radiolabeled with residualizing [89Zr] ZrIV rather than [124I] I optimized post-chemotherapy tumor uptake. Further, PET imaging characteristics were improved by DFOSq rather than DFO-NCS. Therefore, the radionuclide/chelator combination of [89Zr] ZrIV and DFOSq is preferred for the imminent clinical evaluation of chDAB4 as a selective tumor cell death radioligand.

show abstract

Section: Introductionmentioning

confidence: 99%

Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMAB®

Liapis

Tieu

Rudd

et al. 2020

EJNMMI radiopharm. chem.

View full text Add to dashboard Cite

show abstract

“…Current methods for determining tumor responses are based on measuring changes in tumor dimensions using computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound according to Response Evaluation Criteria in Solid Tumors (RECIST) [1] or measuring FDG avidity on 18 F-FDG positron emission tomography (PET)/(PET/CT) scans using PET Response Criteria in Solid Tumors (PERCIST) or tumor-speci c criteria [2,3]. Although there is no established role for FDG-PET in chemotherapy response monitoring of either lung or ovarian cancers [4,5], FDG-PET and SPECT studies in non-small cell lung carcinoma (NSCLC) patients after a rst cycle of platinum-based chemotherapy have been informative.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Positron Emission Tomographic imaging of tumor cell death using Zirconium-89-labeled APOMAB® following cisplatin chemotherapy in lung and ovarian cancer xenograft models

Liapis

Tieu

Wittwer

et al. 2020

Preprint

View full text Add to dashboard Cite

Purpose. There are no currently approved non-invasive methods for detecting tumor treatment responses within the first few days of treatment. The monoclonal antibody, DAB4, or its chimeric derivative, chDAB4 (APOMAB®), targets the Lupus-associated or Sjögren Syndrome-B antigen (La/SSB). La/SSB is over-expressed in malignancy and is selectively targeted by chDAB4 in cancer cells that have died after DNA-damaging treatment. Therefore, chDAB4 could be used to distinguish between chemotherapy responsive and non-responsive patients. In this study, we performed preclinical validation studies using whole-body Positron-Emission Tomography (PET) to examine tumor and normal tissue uptake of 89Zr-labeled chDAB4 in lung or ovarian tumor-bearing mice, which were left untreated or given cisplatin chemotherapy.Methods. The binding of chDAB4 and its conjugates to dead cisplatin-treated human lung and ovarian cancer cells was assessed in vitro as well as its Fc-dependent effector functions. Mice bearing xenografts of H460 lung cancer or A2780 ovarian cancer cells were untreated or given cisplatin chemotherapy followed 24 hours later by 89Zr-labeled chDAB4. Post-cisplatin tumor responses were monitored using bioluminescence imaging and caliper measurements and 89Zr-labeled chDAB4 tumor uptake was measured using an Albira SI PET imager and PMOD analysis software. On completion of experiments, organs were dissected and biodistribution of 89Zr-labeled chDAB4 was measured using a Hidex gamma-counter.Results. The chDAB4 antibody bound only to dead A2780 and H460 cells, and its binding increased with cisplatin treatment in vitro. The chDAB4 antibody did not exhibit Fc-dependent effector functions. Chemotherapy significantly increased uptake of 89Zr-labeled chDAB4 in tumors but not in normal tissues for each tumor model. The greatest differences in average uptake of 89Zr-labeled chDAB4 in subcutaneous tumors were observed 3 days post-cisplatin chemotherapy compared to untreated mice, and before tumor shrinkage was evident.Conclusion. After administration of cisplatin chemotherapy, tumor xenograft uptake of 89Zr-labeled chDAB4 was detected in vivo by PET imaging. Given that the chDAB4 mAb lacked effector activity and that malignant rather than normal tissues were targeted after chemotherapy, these results support clinical development of chDAB4 as both a predictive marker of chemotherapy response and a theranostic imaging agent, which may guide subsequent delivery of chDAB4-directed antibody drug or radio-conjugate anticancer therapies.

show abstract

“…Current methods for determining tumor responses are based on measuring changes in tumor dimensions using computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound according to Response Evaluation Criteria in Solid Tumors (RECIST) [1] or measuring FDG avidity on 18 F-FDG positron emission tomography (PET)/(PET/CT) scans using PET Response Criteria in Solid Tumors (PERCIST) or tumor-specific criteria [2,3]. Although there is no established role for FDG-PET in chemotherapy response monitoring of either lung or ovarian cancers [4,5], FDG-PET and SPECT studies in nonsmall cell lung carcinoma (NSCLC) patients after a first cycle of platinum-based chemotherapy have been informative.…”

Section: Introductionmentioning

confidence: 99%

Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

et al. 2021

View full text Add to dashboard Cite

Purpose Early detection of tumor treatment responses represents an unmet clinical need with no approved noninvasive methods. DAB4, or its chimeric derivative, chDAB4 (APOMAB®) is an antibody that targets the Lupus associated antigen (La/SSB). La/SSB is over-expressed in malignancy and selectively targeted by chDAB4 in cancer cells dying from DNA-damaging treatment. Therefore, chDAB4 is a unique diagnostic tool that detects dead cancer cells and thus could distinguish between treatment responsive and nonresponsive patients. Procedures In clinically relevant tumor models, mice bearing subcutaneous xenografts of human ovarian or lung cancer cell lines or intraperitoneal ovarian cancer xenografts were untreated or given chemotherapy followed 24h later by chDAB4 radiolabeled with [89Zr]ZrIV. Tumor responses were monitored using bioluminescence imaging and caliper measurements. [89Zr]Zr-chDAB4 uptake in tumor and normal tissues was measured using an Albira SI Positron-Emission Tomography (PET) imager and its biodistribution was measured using a Hidex gamma-counter. Results Tumor uptake of [89Zr]Zr-chDAB4 was detected in untreated mice, and uptake significantly increased in both human lung and ovarian tumors after chemotherapy, but not in normal tissues. Conclusion Given that tumors, rather than normal tissues, were targeted after chemotherapy, these results support the clinical development of chDAB4 as a radiodiagnostic imaging agent and as a potential predictive marker of treatment response.

show abstract

RESISTing the Need to Quantify: Putting Qualitative FDG-PET/CT Tumor Response Assessment Criteria into Daily Practice

Cited by 10 publications

References 55 publications

Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMAB®

Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMAB®

WITHDRAWN: Positron Emission Tomographic imaging of tumor cell death using Zirconium-89-labeled APOMAB® following cisplatin chemotherapy in lung and ovarian cancer xenograft models

Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models

Contact Info

Product

Resources

About