Whole body PD-1 and PD-L1 PET with 89Zr-nivolumab and 18F- BMS-986192 in pts with NSCLC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20047-e20047 ◽  
Author(s):  
Anna-Larissa N. Niemeijer ◽  
Egbert F. Smit ◽  
G.a.M.S. van Dongen ◽  
A.D. Windhorst ◽  
Marc C. Huisman ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Tracer Uptake ◽  
Whole Body ◽  
Tumor Uptake ◽  
Treatment Results ◽  
Tumor Biopsy ◽  
Small Clinical Trial ◽  
Tissue Contrast ◽  
Substantial Heterogeneity ◽  
Clinical Trial Information

e20047 Background: Tumor PD-L1 IHC relates moderately with treatment outcome following anti-PD-(L)1 monotherapy in pts with NSCLC. Aim: 1. To assess safety of the PET procedures. 2. To quantify PD-1 and PD-L1 expression in tumors with 89Zirconium-labeled nivolumab (89Zr-nivo) and 18F-labeled BMS-986192 (18F-PD-L1) PET. 3. To assess intra- and inter-patient tracer uptake differences in tumors. 4. To correlate PET results with IHC and treatment outcome. Methods: NSCLC pts eligible for treatment with nivolumab were included. Pts received a dynamic and static whole body 18F-PD-L1 and a static 89Zr-nivo PET scan. A baseline tumor biopsy was required and up to two additional biopsies were allowed in case PET showed heterogeneous tumor uptake. SUVpeak was calculated for all delineable tumor lesions and related to PD-(L)1 IHC (28.8 assay) and response after 6 wks of nivolumab treatment. Results: 7 pts (5 ≥1%, 2 ≥50% and 2 negative by PD-L1 IHC) were enrolled and 11 lesions analyzed. No toxicity related to radiotracer administration was identified. Tumor uptake of both tracers was visualized in all pts. There was substantial variability among pts for 18F-PD-L1 (mean SUV 5.4, range 2.2 - 14.4) and 89Zr-nivo (mean SUV 5.0, range 1.6 - 9.7). Intra-patient tracer uptake heterogeneity was also seen: mean 2.5-fold (±0.96) and 2.3-fold (±0.86) differences between lesions for 18F-PD-L1 and 89Zr-nivo SUV, respectively. For lesions with < 50% PD-L1 IHC mean 18F-PD-L1 SUV was 3.4 (±2.9) as compared to 7.1 (±6.0) for lesions with ≥50% PD-L1 IHC (p = 0.22). For lesions with low PD-1 expression mean 89Zr-nivo SUV was 6.9 (±2.7) as compared to 8.1 (±2.0) for lesions with high PD-1 expression (p = 0.44). Five pts were evaluable for response evaluation: 1 PR, 2 SD and 2 PD with 18F-PD-L1 SUV values (most PET avid lesion) of 14.4 (PR), 2.0 and 5.4 (SD) and 6.4 and 6.6 (PD). Conclusion: 1.PET-imaging with both tracers is safe and feasible, with good tumor-to-normal tissue contrast. 2. Tumor uptake demonstrated substantial heterogeneity among pts and among tumors within the same pts. 3. Although higher 18F-PD-L1 tumor uptake was seen in pts with ≥50% tumor PD-L1 IHC and the highest 18F-PD-L1 SUV was measured in the responding pt, the dataset is still very small. Clinical trial information: 2015-004760-11.

Whole body PD-L1 PET in patients with NSCLC and melanoma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 139-139 ◽  
Author(s):  
David K. Leung ◽  
Joop De Langen ◽  
David Raunig ◽  
Anna-Larissa N. Niemeijer ◽  
Egbert F. Smit ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Intraclass Correlation ◽  
Tracer Uptake ◽  
Whole Body ◽  
Clear Correlation ◽  
Recist 1.1 ◽  
Equal Variance ◽  
Subject Variability ◽  
A Prospective Study ◽  
Clinical Trial Information

139 Background: PD-(L)1 immunotherapy is effective in multiple tumors, including NSCLC and melanoma, but tumor PD-L1 IHC correlates only moderately with treatment outcome. This study aims to assess 1) safety of 18F-BMS-986192 (18F-PD-L1) in human, 2) PD-L1 quantification in tumors using 18F-PD-L1 PET, 3) PD-L1 PET correlation with IHC and treatment outcome, and 4) intra and inter subject tracer uptake variability. Methods: Pts with NSCLC (N = 10) and melanoma (N = 3) were included. At baseline, pts received a static or multiphase dynamic whole body PET scan after injecting 200 MBq 18F-BMS-986192. For NSCLC pts, (1) SUV(max, peak and mean) were measured for each delineable tumor (N = 32, 1-7 tumors/pt), (2) PD-L1 IHC (28.8 assay) was performed on the biopsy, and (3) response to Nivolumab therapy assessed by RECIST 1.1. Intra and inter subject variability and intraclass correlation were calculated using SUVs of all assessed tumors. Equal variance for PD-L1 status was evaluated by a Levene’s test. Four (3 female) pts underwent dosimetry study (ICRP 60). Results: No AEs related to radiotracer was observed. Dosimetry study demonstrated whole body exposure of 30 mGy at dose > 1400 MBq. Biodistribution among pts is comparable. PD-L1 IHC from 13 biopsied lesions were evaluated, 5 < 1%, 4 ≥1%, and 4 ≥50%. Tumor tracer uptake was measured in NSCLC pts and categorized by PDL-1 IHC as ≥50% or < 50%. Clinical trial information: 2015-004760-11. Tumor SUVs did not correlate with RECIST 1.1 assessment. Lesion heterogeneity was reflected in both inter and intra pt variability (CVinter = 41%, CVintra = 53%, ICC = 0.41 for SUVpeak). Levene’s test showed no significance in variability between the two PD-L1 categories. Conclusions: PET-imaging with 18F-BMS-986192 is safe and feasible in pts with NSCLC and melanoma. Pts with higher PD-L1 PET SUV have higher PD-L1 by IHC. Intra pt variability is similar to inter pt variability. With limited number of pts, no clear correlation of PET PD-L1 and tumor response is observed. A prospective study with this tracer is underway to further investigate 18F-BMS-986192 in understanding of PD-L1 expression.[Table: see text]

scholarly journals 64Cu-NODAGA-c(RGDyK) Is a Promising New Angiogenesis PET Tracer: Correlation between Tumor Uptake and Integrin Expression in Human Neuroendocrine Tumor Xenografts

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jytte Oxboel ◽  
Christina Schjoeth-Eskesen ◽  
Henrik H. El-Ali ◽  
Jacob Madsen ◽  
Andreas Kjaer
Keyword(s):  
Gene Expression ◽  
Neuroendocrine Tumor ◽  
Bladder Wall ◽  
Absorbed Dose ◽  
Tracer Uptake ◽  
Whole Body ◽  
Tumor Uptake ◽  
Tumor Xenografts ◽  
Pet Tracer ◽  
Biodistribution Data

Purpose. The purpose of this paper is to evaluate a new PET tracer 64Cu-NODAGA-c(RGDyK) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans. Procedures. Nude mice with human neuroendocrine tumor xenografts (H727) were administered 64Cu-NODAGA-c(RGDyK) i.v. for study of biodistribution as well as for dynamic PET. Gene expression of angiogenesis markers integrin , integrin , and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors (%ID/g). From biodistribution data human radiation-absorbed doses were estimated using OLINDA/EXM. Results. Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake, for integrin  , integrin   and VEGF-A (all ). The whole body effective dose for humans was estimated to be 0.038 and 0.029 mSv/MBq for females and males, respectively, with highest absorbed dose in bladder wall. Conclusion. 64Cu-NODAGA-c(RGDyK) is a promising new angiogenesis PET tracer with potential for human use.

scholarly journals Site-Specific Radiolabeling of a Human PD-L1 Nanobody via Maleimide–Cysteine Chemistry

2021 ◽  
Vol 14 (6) ◽  
pp. 550
Author(s):  
Dora Mugoli Chigoho ◽  
Quentin Lecocq ◽  
Robin Maximilian Awad ◽  
Karine Breckpot ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Ex Vivo ◽  
Tracer Uptake ◽  
Whole Body ◽  
Cancer Therapies ◽  
Tumor Biopsy ◽  
Efficient Treatment ◽  
Site Specific ◽  
Ex Vivo Biodistribution

Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) and its ligand PD-L1 have proven to be efficient cancer therapies in a subset of patients. From all the patients with various cancer types, only 20% have a positive response. Being able to distinguish patients that do express PD-1/PD-L1 from patients that do not allows patients to benefit from a more personalized and efficient treatment of tumor lesion(s). Expression of PD-1 and PD-L1 is typically assessed via immunohistochemical detection in a tumor biopsy. However, this method does not take in account the expression heterogeneity within the lesion, nor the possible metastasis. To visualize whole-body PD-L1 expression by PET imaging, we developed a nanobody-based radio-immunotracer targeting PD-L1 site-specifically labeled with gallium-68. The cysteine-tagged nanobody was site-specifically conjugated with a maleimide (mal)-NOTA chelator and radiolabeling was tested at different nanobody concentrations and temperatures. Affinity and specificity of the tracer, referred to as [68Ga]Ga-NOTA-mal-hPD-L1 Nb, were assayed by surface plasmon resonance and on PD-L1POS or PD-L1NEG 624-MEL cells. Xenografted athymic nude mice bearing 624-MEL PD-L1POS or PD-L1NEG tumors were injected with the tracer and ex vivo biodistribution was performed 1 h 20 min post-injection. Ideal 68Ga-labeling conditions were found at 50 °C for 15 min. [68Ga]Ga-NOTA-mal-hPD-L1 Nb was obtained in 80 ± 5% DC-RCY with a RCP > 99%, and was stable in injection buffer and human serum up to 3 h (>99% RCP). The in vitro characterization showed that the NOTA-functionalized Nb retained its affinity and specificity. Ex vivo biodistribution revealed a tracer uptake of 1.86 ± 0.67% IA/g in the positive tumors compared with 0.42 ± 0.04% IA/g in the negative tumors. Low background uptake was measured in the other organs and tissues, except for the kidneys and bladder, due to the expected excretion route of Nbs. The data obtained show that the site-specific 68Ga-labeled NOTA-mal-hPD-L1 Nb is a promising PET radio-immunotracer due to its ease of production, stability and specificity for PD-L1.

scholarly journals Head-to-head intra-individual comparison of biodistribution and tumor uptake of 68Ga-FAPI and 18F-FDG PET/CT in cancer patients

2021 ◽  
Author(s):  
Frederik L. Giesel ◽  
Clemens Kratochwil ◽  
Joel Schlittenhardt ◽  
Katharina Dendl ◽  
Matthias Eiber ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Standard Of Care ◽  
Blood Pool ◽  
Tracer Uptake ◽  
Time Interval ◽  
Tumor Uptake ◽  
Primary Tumors ◽  
Individual Comparison ◽  
Pet Ct ◽  
Fdg Pet Ct

Abstract Purpose FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of 68Ga-FAPI versus standard-of-care 18F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. Material and Methods This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both 68Ga-FAPI and 18F-FDG PET/CT within a median time interval of 10 days (range 1–89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). Results A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. 68Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for 68Ga-FAPI than 18F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, 68Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. Conclusion Quantitative tumor uptake is comparable between 68Ga-FAPI and 18F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for 68Ga-FAPI. Thus, 68Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological 18F-FDG uptake.

scholarly journals Kezdeti tapasztalatok a 99mTc-PSMA-SPECT/CT-vel prosztatarákos betegekben

2018 ◽  
Vol 159 (35) ◽  
pp. 1433-1440
Author(s):  
István Farkas ◽  
Zsuzsanna Besenyi ◽  
Anikó Maráz ◽  
Zoltán Bajory ◽  
András Palkó ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Bone Scintigraphy ◽  
Transmembrane Protein ◽  
Tracer Uptake ◽  
Whole Body ◽  
Primary Prostate Cancer ◽  
Cancer Tumor ◽  
Visceral Metastases ◽  
Male Patients

Abstract: Introduction: The prostate-specific membrane antigen (PSMA) is a transmembrane protein, that is highly expressed on the surface of prostate cancer cells. In the last few years, several PSMA-specific ligands have been developed, that can be successfully used to detect primary prostate cancer, tumor recurrences and metastases as well. Aim: The goal of our work was to examine the clinical application of a 99mtechnetium-labeled PSMA-radiopharmaceutical as part of the routine diagnostics of prostate cancer. Method: We examined 15 male patients with verified prostate adenocarcinoma with suspicion of progression or recurrence of the disease. We performed whole-body PSMA-SPECT/CTs and multiparametric MRIs of the prostate and the pelvic regions within a week. We used 99mTc-mas3-y-nal-k(Sub-KuE) for the PSMA-SPECT scans. The images were visually evaluated by independent observers. The results were compared with the follow-up bone scintigraphies as well. Results: Twenty-two PSMA-positive lesions were found. Nine of them were localized outside, 13 were within the MRI’s field of view. From these 13 lesions, 7 matched with the SPECT/CT results and in 5 cases the MRI images showed no abnormalities. In one case, bone metastasis was suspected on the MRI scan but there was no corresponding pathological tracer uptake on the SPECT images. In two patients, none of the examinations showed signs of prostate malignancy. Four patients had PSMA-positive bone metastases. One of them had a matching PSMA/SPECT and bone scintigraphy result and in one case the PSMA examination showed metastasis in contrast to the negative bone scintigraphy. Conclusion: PSMA-SPECT/CT with 99mTc-mas3-y-nal-k(Sub-KuE) is a promising diagnostic tool. This technique is capable of visualizing bone metastases and it can detect local recurrences and visceral metastases as well. Orv Hetil. 2018; 159(35): 1433–1440.

scholarly journals Comparative Radioimmunotherapy of Experimental Melanoma with Novel Humanized Antibody to Melanin Labeled with 213Bismuth and 177Lutetium

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 348 ◽  
Author(s):  
Kevin J. H. Allen ◽  
Rubin Jiao ◽  
Mackenzie E. Malo ◽  
Connor Frank ◽  
Darrell R. Fisher ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Ct Imaging ◽  
Whole Body ◽  
Tumor Uptake ◽  
Slowing Down ◽  
Humanized Antibody ◽  
Alpha Emitter ◽  
Systemic Side Effects ◽  
High Tumor Uptake ◽  
Dosimetry Data

Melanoma is a cancer with increasing incidence and there is a need for alternatives to immunotherapy within effective approaches to treatment of metastatic melanoma. We performed comparative radioimmunotherapy (RIT) of experimental B16-F10 melanoma with novel humanized IgG to melanin h8C3 labeled with a beta emitter, 177Lu, and an alpha-emitter, 213Bi, as well as biodistribution, microSPECT/CT imaging, and mouse and human dosimetry calculations. microSPECT/CT imaging showed that a humanized antibody that targets “free” melanin in the tumor microenvironment had high tumor uptake in B16F10 murine melanoma in C57Bl/6 mice, with little to no uptake in naturally melanized tissues. Extrapolation of the mouse dosimetry data to an adult human demonstrated that doses delivered to major organs and the whole body by 177Lu-h8C3 would be approximately two times higher than those delivered by 213Bi-h8C3, while the doses to the tumor would be almost similar. RIT results indicated that 213Bi-h8C3 was more effective in slowing down the tumor growth than 177Lu-h8C3, while both radiolabeled antibodies did not produce significant hematologic or systemic side effects. We concluded that h8C3 antibody labeled with 213Bi is a promising reagent for translation into a clinical trial in patients with metastatic melanoma.

scholarly journals Multiparametric mapping in post-mortem perinatal MRI: a feasibility study

2020 ◽  
Vol 93 (1111) ◽  
pp. 20190952
Author(s):  
Amy R McDowell ◽  
Susan C Shelmerdine ◽  
Sara Lorio ◽  
Wendy Norman ◽  
Rod Jones ◽  
...  
Keyword(s):  
Flip Angle ◽  
Whole Body ◽  
Proton Density ◽  
Single Shot ◽  
Post Mortem ◽  
Variable Flip Angle ◽  
High Quality ◽  
Isotropic Resolution ◽  
Tissue Contrast ◽  
Magnetic Transfer

Objectives: To demonstrate feasibility of a 3 T multiparametric mapping (MPM) quantitative pipeline for perinatal post-mortem MR (PMMR) imaging. Methods: Whole body quantitative PMMR imaging was acquired in four cases, mean gestational age 34 weeks, range (29–38 weeks) on a 3 T Siemens Prisma scanner. A multicontrast protocol yielded proton density, T1 and magnetic transfer (MT) weighted multi-echo images obtained from variable flip angle (FA) 3D fast low angle single-shot (FLASH) acquisitions, radiofrequency transmit field map and one B0 field map alongside four MT weighted acquisitions with saturation pulses of 180, 220, 260 and 300 degrees were acquired, all at 1 mm isotropic resolution. Results: Whole body MPM was achievable in all four foetuses, with R1, R2*, PD and MT maps reconstructed from a single protocol. Multiparametric maps were of high quality and show good tissue contrast, especially the MT maps. Conclusion: MPM is a feasible technique in a perinatal post-mortem setting, which may allow quantification of post-mortem change, prior to being evaluated in a clinical setting. Advances in knowledge: We have shown that the MPM sequence is feasible in PMMR imaging and shown the potential of MT imaging in this setting.

SYNFRIZZ: A first-in-human (FIH) study of a radiolabeled monoclonal antibody (Mab) targeting frizzled homolog 10 (FZD10) in patients (pts) with advanced synovial sarcomas (SyS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11054-11054
Author(s):  
Philippe Alexandre Cassier ◽  
Anne Laure Giraudet ◽  
Chicaco Iwao-Fukukawa ◽  
Gwenaelle Garin ◽  
Jean-Noel Badel ◽  
...  
Keyword(s):  
Objective Response ◽  
Tumor Uptake ◽  
Best Response ◽  
Primary Endpoints ◽  
Clinical Investigations ◽  
Common Grade ◽  
Synovial Sarcomas ◽  
Grade 3 ◽  
To Receive ◽  
Clinical Trial Information

11054 Background: Advanced SyS are rare tumors with limited curative options. FZD10 is highly expressed in SyS but not in normal adult tissue. OTSA101 is a MAb targeting FZD10, labelled with a radioisotope. Methods: We conducted a phase I, FIH study including adult pts with advanced, refractory SyS. In part 1, pts received OTSA101 labelled with In111 used as radiotracer to assess biodistribution and tumor uptake. In part 2, pts with significant tumor uptake were randomized to receive OTSA101 labelled with 370MBq of Y90 (Arm A) or 1110MBq Y90 (Arm B). Primary endpoints were occurrence of unacceptable biodistribution /lack of tumor uptake in part 1 and occurrence of related adverse events (AEs) Grade ≥ 3 during the first 8 weeks following injection of Y90OTSA101 in part 2. Responses were assessed per RECIST 1.1. Results: From January 2012 to June 2015, 20 pts (10 females, median age 43, range 21-67) with advanced SyS were enrolled. Ten pts (50%) had sufficient tumor uptake to proceed to part 2 and 8 were randomized (Arm A: 3 and Arm B: 5). Two pts were not randomized due to worsening PS. During part 2, the most common Grade ≥ 3 AEs were haematological, including reversible lymphopenia, thrombocytopenia and neutropenia, and were more common in Arm B. One pt with SD after 12 weeks received a 2nd injection of 90Y-OTSA101, but experienced fatal hemoptysis. No objective response was observed. Best response was SD in 5/8 pts lasting up to 21 weeks for 1 pt. Conclusions: This FIH shows that radioimmunotherapy targeting FZD10 is feasible and safe in SyS pts. Tumor uptake was heterogeneous but sufficient to select 50% of pts for 90Y-OTSA101 treatment. Due to limited sample size, further clinical investigations are needed to assess the therapeutic activity of 90Y-OTSA101 with a recommended dose of 1110MBq of 90Y. Clinical trial information: NCT01469975.

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