Translational imaging of the Fibroblast Activation Protein (FAP) using the new ligand Ga-68-OncoFAP-DOTAGA

Backhaus, Philipp; Gierse, F.; Burg, Matthias C.; Büther, Florian; Asmus, Inga; Cufe, J.; Dorten, P.; Neri, Dario; Cazzamalli, Samuele; Schäfers, KP; Hermann, Sven; Wagner, Stefan; Breyholz, H. J.; Schäfers, Michael

doi:10.1055/s-0042-1745972

Cited by 3 publications

(6 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FAP-targeted radiopharmaceuticals may revolutionize the field of radioligand imaging of cancer, because of their applicability to many types of malignancies and for the excellent tumour selectivity which has already been proven at the clinical level. (12,13,19) Other SMRC products, 177 Lu-PSMA-617 and Lutathera®, are limited to certain specific cancer indications and may be taken up by certain normal organ structures. (31,32) FAP is mainly expressed in the stroma of solid malignancies, thus adding a new element of differentiation compared to previously established targeting platforms, based on SSTR-2 and PSMA as cellular antigens.…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this this version posted February Proof-of-concept targeting studies with [ 68 Ga]Ga-OncoFAP-DOTAGA ( 68 Ga-OncoFAP), a PET tracer based on OncoFAP, have confirmed excellent biodistribution in patients with different primary and metastatic solid malignancies. (19) Efficacy of radioligand therapeutics is strongly correlated to their residence time in tumours. (9,(20)(21)(22)(23) While Lutathera® and PSMA-617 are characterized by a sustained tumour residence time in patients (i.e., ~61 hours for 177 Lu-PSMA-617 and ~88 hours for 177 Lu-DOTATATE) (24,25), SMRCs based on FAP-targeting agents are typically cleared from solid lesions in few hours.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

et al. 2022

View full text Add to dashboard Cite

Imaging procedures based on small molecule-radio conjugates (SMRCs) targeting fibroblast activation protein (FAP) have recently emerged as a powerful tool for the diagnosis of a wide variety of tumours. However, the therapeutic potential of radiolabeled FAP-targeting agents is limited by their short residence time in neoplastic lesions. In this work, we present the development and in vivo characterization of BiOncoFAP, a new dimeric FAP-binding motif with extended tumour residence time and favorable tumour-to-organ ratio. Methods: The binding properties of BiOncoFAP and its monovalent OncoFAP analogue were assayed against recombinant hFAP. Preclinical experiments with [ 177 Lu]Lu-OncoFAP-DOTAGA ( 177 Lu-OncoFAP) and [ 177 Lu]Lu-BiOncoFAP-DOTAGA ( 177 Lu-BiOncoFAP) were performed in mice bearing FAP-positive HT-1080 tumours.Results: OncoFAP and BiOncoFAP displayed comparable sub-nanomolar dissociation constants towards hFAP in solution, but the bivalent BiOncoFAP bound more avidly to the target immobilized on solid supports. In a comparative biodistribution study, 177 Lu-BiOncoFAP exhibited a more stable and prolonged tumour uptake than 177 Lu-OncoFAP (~20% ID/g vs ~4% ID/g, at 24h p.i., respectively). Notably, 177 Lu-BiOncoFAP showed favorable tumour-to-organ ratios with low kidney uptake. Both 177 Lu-OncoFAP and 177 Lu-BiOncoFAP displayed potent anti-tumour efficacy when administered at therapeutic doses in tumour bearing mice. Conclusions:177 Lu-BiOncoFAP is a promising candidate for radioligand therapy of cancer, with favorable in vivo tumour-to-organ ratio, long tumour residence time and potent anti-cancer efficacy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Accurate determination of the AIF is at the core of most KM approaches, but difficult in small animal PET, specifically in mice. Extracorporeal measurements in arterio-venous shunts using dedicated detectors have been proposed before [ 5 , 6 ], but introduce the need for dispersion correction, especially in circumstances where long catheters are required, e.g. when operating in PET-MRI environments [ 5 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…A common alternative in humans is either manual or automated blood sampling via arterial cannulation. In consideration of the lower total blood volume in small animals, arterio-venous shunt systems involving dedicated extracorporeal blood radioactivity detectors have been established to mirror this clinical approach [ 2 – 4 ] allowing KM with preclinical dynamic PET [ 5 ]. Recently, we have demonstrated this approach to be applicable in the context of small animal perfusion MRI [ 6 ] establishing its use in combined small animal PET-MRI.…”

Section: Introductionmentioning

confidence: 99%

Dispersion-corrected extracorporeal arterial input functions in PET studies of mice: a comparison to intracorporeal microprobe measurements

Cufe,

Gierse,

Schäfers

et al. 2023

EJNMMI Res

View full text Add to dashboard Cite

Background Kinetic modelling of dynamic PET typically requires knowledge of the arterial radiotracer concentration (arterial input function, AIF). Its accurate determination is very difficult in mice. AIF measurements in an extracorporeal shunt can be performed; however, this introduces catheter dispersion. We propose a framework for extracorporeal dispersion correction and validated it by comparison to invasively determined intracorporeal AIFs using implanted microprobes. Results The response of an extracorporeal radiation detector to radioactivity boxcar functions, characterised by a convolution-based dispersion model, gave best fits using double-gamma variate and single-gamma variate kernels compared to mono-exponential kernels for the investigated range of flow rates. Parametric deconvolution with the optimal kernels was performed on 9 mice that were injected with a bolus of 39 ± 25 MBq [18F]F-PSMA-1007 after application of an extracorporeal circulation for three different flow rates in order to correct for dispersion. Comparison with synchronous implantation of microprobes for invasive aortic AIF recordings showed favourable correspondence, with no significant difference in terms of area-under-curve after 300 s and 5000 s. One-tissue and two-tissue compartment model simulations were performed to investigate differences in kinetic parameters between intra- and extracorporeally measured AIFs. Results of the modelling study revealed kinetic parameters close to the chosen simulated values in all compartment models. Conclusion The high correspondence of simultaneously intra- and extracorporeally determined AIFs and resulting model parameters establishes a feasible framework for extracorporeal dispersion correction. This should allow more precise and accurate kinetic modelling in small animal experiments.

show abstract

“…A derivative of FAP, OncoFAP has recently been developed showing improved affinity for malignant tissue (Millul et al 2021). The paper 'Translational Imaging of the Fibroblast activation protein (FAP) using the new ligand [ 68 Ga]Ga-OncoFAP-DOTAGA highlights the first clinical trials and demonstrate its potential (Backhaus et al 2022). The authors first performed pre-clinical studies in murine tumour models expressing FAP which showed better uptake 1 hour post injection when compared to the developed by the University of Heidelberg FAPI-46 ligand, but with similar washout characteristics.…”

Section: By Antonia Denkovamentioning

confidence: 99%

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Toyohara

Al‐Qahtani

Huang

et al. 2022

EJNMMI radiopharm. chem.

View full text Add to dashboard Cite

Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry.

show abstract

Translational imaging of the Fibroblast Activation Protein (FAP) using the new ligand Ga-68-OncoFAP-DOTAGA

Cited by 3 publications

References 1 publication

A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

Dispersion-corrected extracorporeal arterial input functions in PET studies of mice: a comparison to intracorporeal microprobe measurements

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Contact Info

Product

Resources

About