Initial Clinical Results of a Novel Immuno-PET Theranostic Probe in Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer

Abstract

This prospective study evaluated the imaging performance of a novel pretargeting immunologic PET (immuno-PET) method in patients with human epidermal growth factor receptor 2 (HER2)negative, carcinoembryonic antigen (CEA)-positive metastatic breast cancer, compared with CT, bone MRI, and 18 F-FDG PET. Methods: Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq of 68 Ga-IMP288, a histamine-succinyl-glycine peptide given after initial targeting of a trivalent anti-CEA, bispecific, antipeptide antibody. The gold standards were histology and imaging follow-up. Tumor SUVs (SUV max and SUV mean) were measured, and tumor burden was analyzed using total tumor volume and total lesion activity. Results: The total lesion sensitivity of immuno-PET and 18 F-FDG PET were 94.7% (1,116/1,178) and 89.6% (1,056/1,178), respectively. Immuno-PET had a somewhat higher sensitivity than CT or 18 F-FDG PET in lymph nodes (92.4% vs. 69.7% and 89.4%, respectively) and liver metastases (97.3% vs. 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs. 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI or 18 F-FDG PET for bone lesions (95.8% vs. 90.7% and 89.3%, respectively). In contrast to 18 F-FDG PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUV max , SUV mean, and total tumor volume, total lesion activity was significantly higher with immuno-PET than with 18 F-FDG PET (P 5 0.009). Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by 68 Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive metastatic breast cancer patients and warrants further research.

Anti-CEA Pretargeted Immuno-PET Shows Higher Sensitivity Than DOPA PET/CT in Detecting Relapsing Metastatic Medullary Thyroid Carcinoma: Post Hoc Analysis of the iPET-MTC Study

“…The present study reports the high imaging performance of anti-CEA TF2 BsMAb and 68 Ga-IMP288 in metastatic MTC patients, Immuno-PET achieving a 92% overall sensitivity, with a somewhat better sensitivity than CI and DOPA-PET/CT for lymph node, liver, and bone/bone marrow examinations. However, as in a previous study performed in breast cancer patients, Immuno-PET was less effective than CT for lung metastasis detection (25). Sensitivity of DOPA-PET/CT also was low for lung lesion detection in this population.…”

Cucurbituril–Ferrocene: Host–Guest Based Pretargeted Positron Emission Tomography in a Xenograft Model

“…Using the IEDDA pretargeting platform, extended interval times have been shown to result in compromised tumor uptake. , The main drawback of the bispecific antibody (bsAb)-hapten approach is the lack of modularity, requiring the development of a new modified bsAb for every tumor antigen . Furthermore, in clinical trials of the bsAb-hapten platform, immunogenicity of the pretargeting agents has been an issue when anti-inflammatory drugs are not used as part of the pretargeting scheme. − The other two platforms that have been reported are based on streptavidin–biotin binding or oligonucleotide hybridization as the pretargeting interaction. The clinical viability of the streptavidin–biotin methodology is hindered by problems with immunogenicity and the need to use clearing agents. , Finally, the nucleotide hybridization driven pretargeting platform, studied only in preclinical models, has suffered from poor tumor uptake (%ID/g) when full-length antibodies are used for targeting. − While full-length antibodies are currently the primary and most attractive targeting vectors for pretargeting, the nucleotide hybridization approach has shown encouraging results with affibody targeting vectors, suggesting they represent a potentially fruitful alternative. − …”

Radioimmunotherapy for solid tumors: spotlight on Glypican-1 as a radioimmunotherapy target

“…Dose fractionation has been employed successfully, 54 while other approaches such as smaller antibody fragments with shorter half lives are also being tested in the clinic. 55 Pre-targeting approaches are also being investigated preclinically and clinically [56][57][58] ; however, the benefits of a shorter half life need to be weighed against reduced uptake to the tumor. 59 The efficacy of 177 Lutetium ( 177 Lu) using a humanized antibody against prostate specific membrane antigen (PSMA), J591, has been demonstrated in patients with metastatic castrationresistant prostate cancer (mCRPC).…”