Feasibility of PET/CT system performance harmonisation

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Feasibility of PET/CT system performance harmonisation for quantitative multicentre 89Zr studies

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PET/CT Harmonization for Multicenter Studies

Feasibility of PET/CT system performance harmonisation for quantitative multicentre 89Zr studies

Andres Kaalep, Marc Huisman, Terez Sera, Danielle Vugts, Ronald Boellaard, on behalf of EARL, EATRIS and the TRISTAN Consortium


EJNMMI Physics 2018 (5):26 doi: 10.1186/s40658-018-0226-7.

 

Purpose

The aim of this study was to investigate the variability in quantitative performance and feasibility of quantitative harmonisation in 89Zr PET/CT imaging.

Methods

Eight EANM EARL-accredited (Kaalep A et al., Eur J Nucl Med Mol Imaging 45:412-22, 2018) PET/CT systems were investigated using phantom acquisitions of uniform and NEMA NU2-2007 body phantoms. The phantoms were filled according to EANM EARL guidelines for 18F-FDG, but 18F-FDG solution was replaced by a 89Zr calibration mixture. For each system, standard uptake value (SUV) accuracy and recovery coefficients (RC) using SUVmean, SUVmax and SUVpeak metrics were determined.

Results

All eight investigated systems demonstrated similarly shaped RC curves, and five of them exhibited closely aligning recoveries when SUV bias correction was applied. From the evaluated metrics, SUVpeak was found to be least sensitive to noise and reconstruction differences among different systems.

Conclusions

Harmonisation of PET/CT scanners for quantitative 89Zr studies is feasible when proper scanner-dose calibrator cross-calibration and harmonised image reconstruction procedures are followed. An accreditation programme for PET/CT scanners would facilitate multicentre 89Zr quantitative studies.

PET/CT HARMONIZATION FOR MULTICENTER STUDIES
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Integrating molecular nuclear imaging in clinical research

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Integrating molecular nuclear imaging in clinical research to improve anticancer therapy

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Review: PET to improve anti-cancer therapy

Integrating molecular nuclear imaging in clinical research to improve anticancer therapy

Elisabeth G. E. de Vries, Laura Kist de Ruijter, Marjolijn N. Lub-de Hooge, Rudi A. Dierckx, Sjoerd G. Elias & Sjoukje F. Oosting


Nature Reviews Clinical Oncology (2018); doi: 10.1038/s41571-018-0123-y.

Abstract

Effective patient selection before or early during treatment is important to increasing the therapeutic benefits of anticancer treatments. This selection process is often predicated on biomarkers, predominantly biospecimen biomarkers derived from blood or tumour tissue; however, such biomarkers provide limited information about the true extent of disease or about the characteristics of different, potentially heterogeneous tumours present in an individual patient. Molecular imaging can also produce quantitative outputs; such imaging biomarkers can help to fill these knowledge gaps by providing complementary information on tumour characteristics, including heterogeneity and the microenvironment, as well as on pharmacokinetic parameters, drug–target engagement and responses to treatment. This integrative approach could therefore streamline biomarker and drug development, although a range of issues need to be overcome in order to enable a broader use of molecular imaging in clinical trials. In this Perspective article, we outline the multistage process of developing novel molecular imaging biomarkers. We discuss the challenges that have restricted the use of molecular imaging in clinical oncology research to date and outline future opportunities in this area.

REVIEW: PET TO IMPROVE ANTI-CANCER THERAPY
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Development of a CD8 tracer for in vivo evaluation of CD8

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Development of a CD8 tracer for in vivo evaluation of CD8 T cell tumor infiltration during immunotherapy (Conference Abstract)

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Conference Abstract: Tracer for CD8 T-cell tumor infiltration

Development of a CD8 tracer for in vivo evaluation of CD8 T cell tumor infiltration during immunotherapy (Conference Abstract)

René Raavé, Milou Boswinkel, Gerwin Sandker, Peter Wierstra, Erik H. J. G. Aarntzen, Sandra Heskamp


EMIM 2019, Glasgow: #858. EMIM 2019 Abstracts.

Abstract

Introduction

Immunotherapy is considered a hallmark in cancer treatment by its profound and durable clinical responses in patients with various types of cancer. However, only a subgroup of patients responds to immunotherapy and methods for accurate early response monitoring are lacking. Noninvasive quantitative imaging of CD8+ cytotoxic T cells can provide dynamic and spatial information of anti-tumor response. In the present study we characterized an 111In-labeled anti-mouse CD8 antibody for imaging of tumor infiltrating CD8+ cytotoxic T cells in vitro and in vivo in mice bearing murine CT26 colon tumors.

Methods

An anti-mouse CD8 antibody (clone: YTS 169.4) was randomly conjugated with a 30 times molar excess of NCS-DTPA and radiolabeled with 111In. Using CD8+ TK1 mice lymphoma cells, the immunoreactivity, IC50, internalization and affinity characteristics were determined. CT26 tumor bearing BALB/c mice (10-12 weeks old) were intravenously injected with 8.5 µg (8.5 MBq) [111In]In-DTPA-anti-CD8. One group received an excess of non-radiolabeled CD8 antibody (250 µg). SPECT/CT imaging was performed and organs were collected to quantify tracer uptake at 4h, 24h, 48h and 72h after injection. Autoradiography and immunohistochemistry were performed on paraffin embedded tissue sections of tumor, spleen, lymph nodes and duodenum.

Results/Discussion

In vitro assays demonstrated that the immunoreactive fraction was 44%, IC50 was 1.77 nM, Kd was 3.83 nM, and 6.5% internalization of the total membrane bound activity after 4.5 h of incubation. CD8+ T cell containing organs (lymph nodes, spleen and duodenum) were clearly visible on SPECT scans of mice injected with [111In]In-DTPA-CD8-antibody at all time points. Mice that received an excess of non-radiolabeled CD8-antibody showed most uptake in the spleen. Low to moderate tumor uptake was visible in all groups. Ex vivo biodistribution data confirmed results from SPECT imaging. In the lymph nodes, spleen, duodenum and tumor, an uptake of 38.6 ± 12.3% ID/g (±SD), 87.1 ± 18.0% ID/g, 31.7 ± 16.9% ID/g, and 12.9 ±2.9% ID/g at 24h after injection, respectively. The tumor-to-blood ratio increased from 0.48 at 4h after injection to 2.23 at 72h after injection. Autoradiography and immunohistochemistry confirmed these findings.

Conclusions

The CD8 antibody showed specific uptake in CD8+ T cell containing tissues in vivo, but uptake in the tumor was limited because of presence low number of CD8+ T cells. In the future, this tracer has potential for in vivo evaluation of CD8+ T cell infiltration in tumors and lymphoid tissues before and during immunotherapy.

CONFERENCE ABSTRACT: TRACER FOR CD8 T-CELL TUMOR INFILTRATION
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Evaluation of novel 89Zr chelators and corresponding

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Evaluation of novel 89Zr chelators and corresponding 89Zr-labeled immunoconjugates (Conference Abstract)

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Conference Abstract: Novel 89Zr chelators and immunoconjugates

Evaluation of novel 89Zr chelators and corresponding 89Zr-labeled immunoconjugates (Conference Abstract)

Pierre Adumeau, René Raavé, Christian B. Jacobsen, Gerwin Sandker, Sandra Heskamp, Otto Boerman, Mark Rijpkema, Floriane Mangin, Michel Meyer, Jean-Claude Chambron, Mathieu Moreau, Claire Bernhard, Adrien Dubois, Laurène Da Costa, Victor Goncalves, Franck Denat


EMIM 2019, Glasgow, #654. EMIM 2019 Abstracts.

Abstract

Introduction

For immunoPET with 89Zr, the current gold standard to label antibodies is desferrioxamine (DFO).1 However, preclinical studies have shown that the 89Zr-DFO complex is partly unstable in vivo, leading to 89Zr release and subsequent accumulation in mineral bone. This bone uptake may impede the detection of bone metastases, and hampers accurate estimation of the radiation dose to the bone marrow in dose planning for radioimmunotherapy. Therefore, there is a need for more stable 89Zr chelators.

Methods

We have synthesized new octacoordinating 89Zr-bifunctional chelating agents derivated from the DFO* chelator.2 These new chelators were synthesized by coupling different hydroxamic acid-bearing arms to DFO, followed by the introduction of an isothiocyanate moiety. The model antibody trastuzumab was conjugated to the NCS-derivated chelators and DFO-pPhe-NCS as a reference, and radiolabeled with 89Zr. The stability of the radiolabeled chelators and radiolabeled conjugates were evaluated in human plasma, and in PBS in presence of EDTA or DFO. The in vitro behavior of the most promising compounds was investigated more thoroughly using HER2-experessing SK-OV3 cells, and in vivo distribution was studied in mice with subcutaneous SK-OV3 xenografts by PET/CCT imaging and ex vivo tissue analysis.

Results/Discussion

The bifunctional chelators were conjugated efficiently to trastuzumab. Radiolabeling of the conjugates with 89Zr yielded the radioconjugates with high yield, purity and specific activity (RCY >95%, RCP >99%, SA >100 MBq/mg). When challenged with EDTA or DFO, the 89Zr-chelates and the corresponding radioconjugates displayed an improved stability compared to 89Zr-DFO and 89Zr-DFO-trastuzumab, with the best results obtained for the chelator dubbed cycloDFO*. The immunoreactive fraction and IC50 were similar for 89Zr-DFO-trastuzumab and 89Zr-cycloDFO*-trastuzumab. Internalisation after 2h was significantly higher for 89Zr-cycloDFO*-trastuzumab compared to 89Zr-DFO-trastuzumab. Accumulation of 89Zr in bone was significantly lower for 89Zr-DFO-cyclo*-trastuzumab compared to 89Zr-DFO-trastuzumab in knee (3.6 ± 0.4% vs 5.9 ±0.6%), femur (2.2 ± 0.2% vs 3.4 ± 0.3%), and sternum (3.5± 0.4% vs 4.5 ±0.4%) at 72 h after injection. Uptake in the SK-OV3 tumor was similar for both antibody conjugates.

Conclusions

The new 89Zr-chelators and the associated radioconjugates show improved in vitro stability compared to DFO and 89Zr-DFO-trastuzumab. The radioconjugate derivated from the more promising chelator, 89Zr-cycloDFO*-trastuzumab, demonstrated a better in vivo stability compared to 89Zr-DFO-trastuzumab. Therefore, less radiation exposure to bone marrow and improved bone metastasis detection could be achieved using cycloDFO*.

References

1 S. Heskamp, R. Raavé, O. Boerman, M. Rijpkema, V. Goncalves, F. Denat, Bioconjugate Chem., 2017, 28, 2211-2223.

2 D. Vugts, C. Klaver, C. Sewing, A. Poot, K. Adamzek; S. Huegli, C. Mari, G. Visser, I. Valverde, G. Gasser, T. Mindt, G. van Dongen, Eur. J. Nucl. Med. Mol. Imaging, 2017, 44, 286-295

CONFERENCE ABSTRACT: NOVEL 89ZR CHELATORS AND IMMUNOCONJUGATES
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Direct comparison of the in vitro and in vivo stability

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Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET.

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89Zr-DFO Derivative Stability

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET.

René Raavé, Gerwin Sandker, Pierre Adumeau, Christian Borch Jacobsen, Floriane Mangin, Michel Meyer, Mathieu Moreau, Claire Bernhard, Laurène Da Costa, Adrien Dubois, Victor Goncalves, Magnus Gustafsson, Mark Rijpkema, Otto Boerman, Jean-Claude Chambron, Sandra Heskamp, Franck Denat


European Journal of Nuclear Medicine and Molecular Imaging August 2019, Volume 46, Issue 9, pp 1966–1977 doi:10.1007/s00259-019-04343-2.

 

Abstract

 

Currently, the most commonly used chelator for labelling antibodies with 89Zr for immunoPET is desferrioxamine B (DFO). However, preclinical studies have shown that the limited in vivo stability of the 89Zr-DFO complex results in release of 89Zr, which accumulates in mineral bone. Here we report a novel chelator DFOcyclo*, a preorganized extended DFO derivative that enables octacoordination of the 89Zr radiometal. The aim was to compare the in vitro and in vivo stability of [89Zr]Zr-DFOcyclo*, [89Zr]Zr-DFO* and [89Zr]Zr-DFO.

Methods

The stability of 89Zr-labelled chelators alone and after conjugation to trastuzumab was evaluated in human plasma and PBS, and in the presence of excess EDTA or DFO. The immunoreactive fraction, IC50, and internalization rate of the conjugates were evaluated using HER2-expressing SKOV-3 cells. The in vivo distribution was investigated in mice with subcutaneous HER2+ SKOV-3 or HER2− MDA-MB-231 xenografts by PET/CT imaging and quantitative ex vivo tissue analyses 7 days after injection.

Results

89Zr-labelled DFO, DFO* and DFOcyclo* were stable in human plasma for up to 7 days. In competition with EDTA, DFO* and DFOcyclo* showed higher stability than DFO. In competition with excess DFO, DFOcyclo*-trastuzumab was significantly more stable than the corresponding DFO and DFO* conjugates (p < 0.001). Cell binding and internalization were similar for the three conjugates. In in vivo studies, HER2+ SKOV-3 tumour-bearing mice showed significantly lower bone uptake (p < 0.001) 168 h after injection with [89Zr]Zr-DFOcyclo*-trastuzumab (femur 1.5 ± 0.3%ID/g, knee 2.1 ± 0.4%ID/g) or [89Zr]Zr-DFO*-trastuzumab (femur 2.0 ± 0.3%ID/g, knee 2.68 ± 0.4%ID/g) than after injection with [89Zr]Zr-DFO-trastuzumab (femur 4.5 ± 0.6%ID/g, knee 7.8 ± 0.6%ID/g). Blood levels, tumour uptake and uptake in other organs were not significantly different at 168 h after injection. HER2− MDA-MB-231 tumour-bearing mice showed significantly lower tumour uptake (p < 0.001) after injection with [89Zr]Zr-DFOcyclo*-trastuzumab (16.2 ± 10.1%ID/g) and [89Zr]Zr-DFO-trastuzumab (19.6 ± 3.2%ID/g) than HER2+ SKOV-3 tumour-bearing mice (72.1 ± 14.6%ID/g and 93.1 ± 20.9%ID/g, respectively), while bone uptake was similar.

Conclusion

89Zr-labelled DFOcyclo* and DFOcyclo*-trastuzumab showed higher in vitro and in vivo stability than the current commonly used 89Zr-DFO-trastuzumab. DFOcyclo* is a promising candidate to become the new clinically used standard chelator for 89Zr immunoPET.

89ZR-DFO DERIVATIVE STABILITY
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Clinical-grade N-(4-[18F]fluorobenzoyl)-interleukin-2 for PET

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Clinical-grade N-(4-[18F]fluorobenzoyl)-interleukin-2 for PET imaging of activated T-cells in humans

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18F-IL2 for clinical PET

Clinical-grade N-(4-[18F]fluorobenzoyl)-interleukin-2 for PET imaging of activated T-cells in humans

Elly L. van der Veen, Inês F. Antunes, Petra Maarsingh, Janet Hessels-Scheper, Rolf Zijlma, Hendrikus H. Boersma, Annelies Jorritsma-Smit, Geke A. P. Hospers, Elisabeth G. E. de Vries, Marjolijn N. Lub-de Hooge, Erik F. J. de Vries


EJNMMI Radiopharmacy and Chemistry, Dec 2019, 4,15. doi: 10.1186/s41181-019-0062-7.

Abstract

Background

Molecular imaging of immune cells might be a potential tool for response prediction, treatment evaluation and patient selection in inflammatory diseases as well as oncology. Targeting interleukin-2 (IL2) receptors on activated T-cells using positron emission tomography (PET) with N-(4-[18F]fluorobenzoyl)-interleukin-2 ([18F]FB-IL2) could be such a strategy. This paper describes the challenging translation of the partly manual labeling of [18F]FB-IL2 for preclinical studies into an automated procedure following Good Manufacturing Practices (GMP), resulting in a radiopharmaceutical suitable for clinical use.

Methods

The preclinical synthesis of [18F]FB-IL2 was the starting point for translation to a clinical production method. To overcome several challenges, major adaptations in the production process were executed. The final analytical methods and production method were validated and documented. All data with regards to the quality and safety of the final drug product were documented in an investigational medicinal product dossier.

Results

Restrictions in the [18F]FB-IL2 production were imposed by hardware configuration of the automated synthesis equipment and by use of disposable cassettes. Critical steps in the [18F]FB-IL2 production comprised the purification method, stability of recombinant human IL2 and the final formulation. With the GMP compliant production method, [18F]FB-IL2 could reliably be produced with consistent quality complying to all specifications.

Conclusions

To enable the use of [18F]FB-IL2 in clinical studies, a fully automated GMP compliant production process was developed. [18F]FB-IL2 is now produced consistently for use in clinical studies.

18F-IL2 FOR CLINICAL PET
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Ga-NODAGA-IL2 for imaging activated T-cells

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[Ga-68]Ga-NODAGA-IL2 for imaging activated T-cells. (Conference Abstract)

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Conference Abstract: 68Ga-NODAGA-IL2 for T-cell imaging

[Ga-68]Ga-NODAGA-IL2 for imaging activated T-cells. (Conference Abstract)

Antunes, I., van der Veen, E. L., Suurs, F. V., Dierckx, R. A. J. O., Lub-de Hooge, M. N., de Vries, E. G. E. & de Vries, E. F. J.


Oct-2019, In : European Journal of Nuclear Medicine and Molecular Imaging. 46, SUPPL 1, p. S702 1 p.

32nd Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) - Barcelona, Spain Duration: 12-Oct-2019 - 16-Oct-2019

CONFERENCE ABSTRACT: 68GA-NODAGA-IL2 FOR T-CELL IMAGING
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Tracers for non-invasive radionuclide imaging of immune

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Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

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PET tracers for immune checkpoint imaging

Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

Peter Wierstra, Gerwin Sandker, Erik Aarntzen, Martin Gotthardt, Gosse Adema, Johan Bussink, René Raavé & Sandra Heskamp.


EJNMMI Radiopharmacy and Chemistry volume 4,29 (2019). doi: 10.1186/s41181-019-0078-z.

Abstract

Immunotherapy with checkpoint inhibitors demonstrates impressive improvements in the treatment of several types of cancer. Unfortunately, not all patients respond to therapy while severe immune-related adverse effects are prevalent. Currently, patient stratification is based on immunotherapy marker expression through immunohistochemical analysis on biopsied material. However, expression can be heterogeneous within and between tumor lesions, amplifying the sampling limitations of biopsies. Analysis of immunotherapy target expression by non-invasive quantitative molecular imaging with PET or SPECT may overcome this issue. In this review, an overview of tracers that have been developed for preclinical and clinical imaging of key immunotherapy targets, such as programmed cell death-1, programmed cell death ligand-1, IDO1 and cytotoxic T lymphocyte-associated antigen-4 is presented. We discuss important aspects to consider when developing such tracers and outline the future perspectives of molecular imaging of immunotherapy markers..

PET TRACERS FOR IMMUNE CHECKPOINT IMAGING
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Synthesis and Evaluation of Zirconium-89 Labelled

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Synthesis and Evaluation of Zirconium-89 Labelled and Long-Lived GLP-1 Receptor Agonists for PET Imaging

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89Zr labeled long lived GLP-1 receptor agonist

Synthesis and Evaluation of Zirconium-89 Labelled and Long-Lived GLP-1 Receptor Agonists for PET Imaging

Christian Borch Jacobsen, René Raavé, Marie Østergaard Pedersen, Pierre Adumeau, Mathieu Moreau, Ibai Valverde, Inga Bjørnsdottir, Jesper Bøggild Kristensen, Mette Finderup Grove, Kirsten Raun, James McGuire, Victor Goncalves, Sandra Heskamp, Franck Denat, Magnus Gustafsson


Nuclear Medicine and Biology 2019 Dec 4. doi: 10.1016/j.nucmedbio.2019.11.006.

Abstract

Introduction

Lately, zirconium-89 has shown great promise as a radionuclide for PET applications of long circulating biomolecules. Here, the design and synthesis of protracted and long-lived GLP-1 receptor agonists conjugated to desferrioxamine and labelled with zirconium-89 is presented with the purpose of studying their in vivo distribution by PET imaging. The labelled conjugates were evaluated and compared to a non-labelled GLP-1 receptor agonist in both in vitro and in vivo assays to certify that the modification did not significantly alter the peptides' structure or function. Finally, the zirconium-89 labelled peptides were employed in PET imaging, providing visual verification of their in vivo biodistribution.

Methods

The evaluation of the radiolabelled peptides and comparison to their non-labelled parent peptide was performed by in vitro assays measuring binding and agonistic potency to the GLP-1 receptor, physicochemical studies aiming at elucidating change in peptide structure upon bioconjugation and labelling as well as an in vivo food in-take study illustrating the compounds' pharmacodynamic properties. The biodistribution of the labelled GLP-1 analogues was determined by ex vivo biodistribution and in vivo PET imaging.

Results

The results indicate that it is surprisingly feasible to design and synthesize a protracted, zirconium-89 labelled GLP-1 receptor agonist without losing in vitro potency or affinity as compared to a non-labelled parent peptide. Physicochemical properties as well as pharmacodynamic properties are also maintained. The biodistribution in rats show high accumulation of radiolabelled peptide in well-perfused organs such as the liver, kidney, heart and lungs. The PET imaging study confirmed the findings from the biodistribution study with a significant high uptake in kidneys and presence of activity in liver, heart and larger blood vessels.

Conclusions and advances in knowledge

This initial study indicates the potential to monitor the in vivo distribution of long-circulating incretin hormones using zirconium-89 based PET.

89ZR LABELED LONG LIVED GLP-1 RECEPTOR AGONIST
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PET of 89Zr-Pembrolizumab in Cynomolgus

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PET/CT Imaging of 89Zr-N-sucDf-Pembrolizumab in Healthy Cynomolgus Monkeys

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PET of 89Zr-Pembrolizumab in Cynomolgus

PET/CT Imaging of 89Zr-N-sucDf-Pembrolizumab in Healthy Cynomolgus Monkeys

Wenping Li, Yuchuan Wang, Daniel Rubins, Idriss Bennacef, Marie Holahan, Hyking Haley, Mona Purcell, Liza Gantert, SuChun Hseih, Michael Judo, Wolfgang Seghezzi, Shuli Zhang, Elly L. van der Veen, Marjolijn N. Lub-de Hooge, Elisabeth G.E. de Vries, Jeffrey L. Evelhoch, Michael Klimas, Eric D. Hostetler


Molecular Imaging and Biology 2020 Oct 26. doi: 10.1007/s11307-020-01558-w

Abstract

Purpose:

Programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) are the targets for immunotherapy in many cancer types. Although PD-1 blockade has therapeutic effects, the efficacy differs between patients. Factors contributing to this variability are PD-L1 expression levels and immune cells present in tumors. However, it is not well understood how PD-1 expression in the tumor microenvironment impacts immunotherapy response. Thus, imaging of PD-1-expressing immune cells is of interest. This study aims to evaluate the biodistribution of Zirconium-89 (89Zr)-labeled pembrolizumab, a humanized IgG4 kappa monoclonal antibody targeting PD-1, in healthy cynomolgus monkeys as a translational model of tracking PD-1- positive immune cells.

Procedures:

Pembrolizumab was conjugated with the tetrafluorophenol-N-succinyl desferal- Fe(III) ester (TFP-N-sucDf) and subsequently radiolabeled with 89Zr. Four cynomolgus monkeys with no previous exposure to humanized monoclonal antibodies received tracer only or tracer co-injected with pembrolizumab intravenously over 5 min. Thereafter, a static whole-body positron emission tomography (PET) scan was acquired with 10 min per bed position on days 0, 2, 5, and 7. Image-derived standardized uptake values (SUVmean) were quantified by region of interest (ROI) analysis.

Results:

89Zr-N-sucDf-pembrolizumab was synthesized with high radiochemical purity (>99 %) and acceptable molar activity (>7 MBq/nmol). In animals dosed with tracer only, 89Zr-N-sucDf-pembrolizumab distribution in lymphoid tissues such as mesenteric lymph nodes, spleen, and tonsils increased over time. Except for the liver, low radiotracer distribution was observed in all non-lymphoid tissue including the lung, muscle, brain, heart, and kidney. When a large excess of pembrolizumab was co-administered with a radiotracer, accumulation in the lymph nodes, spleen, and tonsils was reduced, suggestive of target-mediated accumulation.

Conclusions:

89Zr-N-sucDf-pembrolizumab shows preferential uptake in the lymphoid tissues including the lymph nodes, spleen, and tonsils. 89Zr-N-sucDf-pembrolizumab may be useful in tracking the distribution of a subset of immune cells in non-human primates and humans.

Trial registration:

ClinicalTrials.gov; Identifier: NCT02760225

PET of 89Zr-Pembrolizumab in Cynomolgus
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