Anti-PSMA 124I-scFvD2B as a new immuno-PET tool for prostate cancer: preclinical proof of principle

B Frigerio,A Alessi,E Seregni,A Lorenzoni,C Chiesa,E Luison,R Valdagni,A Bogni,S Canevari,S Morlino,A Satta,M Figini,M Mira

doi:10.1186/s13046-019-1325-6

Abstract

BackgroundProstate cancer (PCa) is the second leading cause of cancer-related death in the Western population. The use in oncology of positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease and detection of metastatic lesions. Prostate-specific membrane antigen (PSMA) expression, directly related to androgen-independence, metastasis and progression, renders this tumour associate antigen a good target for the development of new radiopharmaceuticals for PET. Aim of this study was to demonstrate in a preclinical in vivo model (PSMA-positive versus PSMA-negative tumours) the targeting specificity and sensitivity of the anti-PSMA single-chain variable fragment (scFv) labelled with 124I.MethodsThe 124I-labeling conditions of the antibody fragment scFvD2B were optimized and assessed for purity and immunoreactivity. The specificity of 124I-scFvD2B was tested in mice bearing PSMA-positive and PSMA-negative tumours to assess both ex-vivo biodistribution and immune-PET.ResultsThe uptake fraction of 124I-scFvD2B was very high on PSMA positive cells (range 75–91%) and highly specific and immuno-PET at the optimal time point, defined between 15 h and 24 h, provides a specific localization of lesions bearing the target antigen of interest (PSMA positive vs PSMA negative tumors %ID/g: p = 0.0198 and p = 0.0176 respectively) yielding a median target/background ratio around 30–40.ConclusionsPreclinical in vivo results of our immuno-PET reagent are highly promising. The target to background ratio is improved notably using PET compared to SPECT previously performed.These data suggest that, upon clinical confirmation of sensitivity and specificity, our anti-PSMA 124I-scFvD2B may be superior to other diagnostic modalities for PCa. The possibility to combine in patients our 124I-scFvD2B in multi-modal systems, such as PET/CT, PET/MR and PET/SPECT/CT, will provide quantitative 3D tomographic images improving the knowledge of cancer biology and treatment.

Highlights

Prostate cancer (PCa) is the second leading cause of cancer-related death in the Western population
Against Prostate-specific membrane antigen (PSMA) we developed a very promising monoclonal antibody and the derived scFvD2B able to localize tumours in different mouse models [17,18,19,20]
Cell lines were subjected to short tandem repeat (STR) analysis in accordance with the American Type Culture Collection (ATCC) guidelines, and the genetic profiles were compared to publically available databases to verify authenticity

Summary

Introduction

Prostate cancer (PCa) is the second leading cause of cancer-related death in the Western population. Conventional anatomical imaging modalities initially used were ultrasound, computed tomography (CT), bone scintigraphy, and magnetic resonance imaging (MRI) These techniques may offer information on morphological tumors, but they have considerable limitations for staging and monitoring the disease, especially in patients with low PSA levels [4, 5]. PET or PET/CT use of [18F]FDG is limited in PCa [7]; PCa glucose utilization is low, and FDG uptake is insufficient in up to 81% of primary tumors [8, 9] Other metabolic tracers, such as [11C]Choline- or [18F]Fluorocholine, have shown some promising results in the clinic but choline uptake was detected in malignant and in hyperplastic prostate tissues [10]

Methods

Results

Discussion

Conclusion