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.

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.

scholarly journals Neuroblastoma xenograft models demonstrate the therapeutic potential of 177Lu-octreotate

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Arman Romiani ◽  
Johan Spetz ◽  
Emman Shubbar ◽  
Dan E. Lind ◽  
Bengt Hallberg ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Cell Lines ◽  
Therapeutic Potential ◽  
Somatostatin Receptors ◽  
Absorbed Dose ◽  
Tumor Xenograft ◽  
Activity Levels ◽  
Tumor Type ◽  
Tumor Xenografts ◽  
Concentration Levels

Abstract Background Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants. NB is a neuroendocrine tumor type with various characteristics and features, and with diverse outcome. The most malignant NBs have a 5-year survival rate of only 40–50%, indicating the need for novel and improved treatment options. 177Lu-octreotate is routinely administered for treatment of neuroendocrine tumors overexpressing somatostatin receptors (SSTR). The aim of this study was to examine the biodistribution of 177Lu-octreotate in mice bearing aggressive human NB cell lines, in order to evaluate the potential usefulness of 177Lu-octreotate for treatment of NB. Methods BALB/c nude mice bearing CLB-BAR, CLB-GE or IMR-32 tumor xenografts (n = 5–7/group) were i.v. injected with 0.15 MBq, 1.5 MBq or 15 MBq 177Lu-octreotate and sacrificed 1 h, 24 h, 48 h and 168 h after administration. The radioactivity concentration was determined for collected tissue samples, tumor-to-normal-tissue activity concentration ratios (T/N) and mean absorbed dose for each tissue were calculated. Immunohistochemical (IHC) staining for SSTR1–5, and Ki67 were carried out for tumor xenografts from the three cell lines. Results High 177Lu concentration levels and T/N values were observed in all NB tumors, with the highest for CLB-GE tumor xenografts (72%IA/g 24 h p.i.; 1.5 MBq 177Lu-octreotate). The mean absorbed dose to the tumor was 6.8 Gy, 54 Gy and 29 Gy for CLB-BAR, CLB-GE and IMR-32, respectively, p.i. of 15 MBq 177Lu-octreotate. Receptor saturation was clearly observed in CLB-BAR, resulting in higher concentration levels in the tumor when lower activity levels where administered. IHC staining demonstrated highest expression of SSTR2 in CLB-GE, followed by CLB-BAR and IMR-32. Conclusion T/N values for all three human NB tumor xenograft types investigated were high relative to previously investigated neuroendocrine tumor types. The results indicate a clear potential of 177Lu-octreotate as a therapeutic alternative for metastatic NB.

scholarly journals Evaluation of Radiation dosimetry of 99mTc-HYNIC-PSMA and imaging in prostate cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jianping Zhang ◽  
Jiangang Zhang ◽  
Xiaoping Xu ◽  
Linjun Lu ◽  
Silong Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Dosimetry ◽  
Tumor Imaging ◽  
Absorbed Dose ◽  
Ct Images ◽  
Tracer Uptake ◽  
Whole Body ◽  
Imaging Method ◽  
Absorbed Doses ◽  
Total Body

Abstract This study aims to evaluate the radiation dosimetry of a new technetium-99m‒labelled small-molecule inhibitor of prostate-specific membrane antigen (HYNIC-Glu-Urea-A, 99mTc-HYNIC-PSMA) and its feasibility as a tumor-imaging agent in prostate cancer (PCa) patients. A total of 15 PCa patients were enrolled in this study. For the dosimetry study, 5 PCa patients received whole-body planar scans at 0.5 h, 1 h, 2 h, 4 h and 8 h after 99mTc-HYNIC-PSMA injection. The Dosimetry Toolkit (GE, Milwaukee) was used to process the data and segment the organs in the SPECT/CT images, which were then projected onto planar images. The organ-specific absorbed doses, total-body absorbed doses and 99mTc-HYNIC-PSMA effective doses of patients were calculated using OLINDA/EXM 1.1 software. Whole-body SPECT/CT images were also acquired from additional 10 prostate patients to investigate the feasibility of 99mTc-HYNIC-PSMA for imaging tumors by calculating the ratio of tumor-to-background tracer uptake at 2 h after 740 MBq administration. The total-body absorbed dose was 1.54E-03 ± 2.43E-04 mGy/MBq, and the effective dose was 3.72E-03 ± 4.5E-04 mSv/MBq. Compared to published studies of other similar PSMA tracers and 99mTc-targeted conventional tracers, the absorbed doses of 99mTc-HYNIC-PSMA in all organs showed that it could be used safely in the human body. In addition, 99mTc-HYNIC-PSMA showed high tracer uptake (with a tumor-to-background ratio of 9.42 ± 2.62) in the malignant lesions of PCa patients, making it a promising radiopharmaceutical imaging method for site-specific management of PCa.

Dosimetric measurements of 68Ga-High Affinity DOTATATE

2014 ◽  
Vol 53 (05) ◽  
pp. 211-216 ◽  
Author(s):  
R Freudenberg ◽  
L. Oehme ◽  
K. Zöphel ◽  
M. Schottelius ◽  
H.-J. Wester ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Radiation Dosimetry ◽  
Somatostatin Receptor ◽  
Bladder Wall ◽  
Absorbed Dose ◽  
Whole Body ◽  
Radioactivity Concentration ◽  
Receptor Scintigraphy ◽  
Urinary Bladder Wall ◽  
Background Contrast

SummaryPurpose: 68Ga-labelled compounds are increasingly used for somatostatin-receptor scintigraphy because of their favourable biokinetic properties, a higher tumour-to- background contrast and higher diagnostic accuracy compared to the gamma-emitting tracer 111In-DTPA-octreotide. Recently, we have introduced the new tracer 68Ga-DOTA- 3-iodo-Tyr3-Thr8-octreotide (68Ga-HA-DOTA- TATE). The present study demonstrates the biodistribution and radiation dosimetry of this tracer in humans. Patients, methods: Seven men were enrolled in this analysis. Every patient underwent a 20 min dynamic PET scan after intravenous injection of about 114 ± 9 MBq of 68Ga-HA-DOTATATE. This was followed by two whole-body scans at 30 min p. i. and 120 min p. i. Blood radioactivity concentration was determined non-invasively from a ROI drawn over the aorta. Urine was collected until the time of the last scan. Liver, spleen, kidneys and urinary bladder wall were included in the dosimetric estimation that was carried out with the software package OLINDA 1.0. Results: Physiological 68Ga- HA-DOTATATE uptake was observed in the pituitary gland, thyroid, salivary glands, liver, spleen, kidneys, urinary bladder, adrenals and intestine. Organs with the highest absorbed dose were spleen (0.26 ± 0.11 mSv/MBq), kidneys (0.14 ± 0.03 mSv/MBq) and liver (0.12 ± 0.02 mSv/MBq).The estimated effective dose was 0.024 ± 0.001 mSv/MBq. Conclusion: Our study demonstrates biokinetics and radiation exposure of the 68Ga-labelled tracer HA-DOTATATE to be comparable to other 68Ga-labelled SSR analogues in clinical use.

scholarly journals Biodistribution and post-therapy dosimetric analysis of [177Lu]Lu-DOTAZOL in patients with osteoblastic metastases: first results

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ambreen Khawar ◽  
Elisabeth Eppard ◽  
Frank Roesch ◽  
Hojjat Ahmadzadehfar ◽  
Stefan Kürpig ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Radionuclide Therapy ◽  
Bladder Wall ◽  
Absorbed Dose ◽  
Whole Body ◽  
Normal Organ ◽  
Skeletal Disease ◽  
Absorbed Doses ◽  
Urinary Bladder Wall ◽  
Dosimetric Analysis

Abstract Background Preclinical biodistribution and dosimetric analysis of [177Lu]Lu-DOTAZOL suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [177Lu]Lu-DOTAZOL in patients with metastatic skeletal disease. Method Four patients with metastatic skeletal disease (age range, 64–83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [177Lu]Lu-DOTAZOL. Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier’s dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose. Results Qualitative biodistribution analysis revealed early and high uptake of [177Lu]Lu-DOTAZOL in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [177Lu]Lu-DOTAZOL are consistent with preclinical data. Conclusion [177Lu]Lu-DOTAZOL shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [177Lu]Lu-DOTAZOL in the clinical setting.

scholarly journals Human biodistribution and dosimetry of [11C]-UCB-J, a PET radiotracer for imaging synaptic density

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Christopher Cawthorne ◽  
Paul Maguire ◽  
Joel Mercier ◽  
David Sciberras ◽  
Kim Serdons ◽  
...  
Keyword(s):  
Effective Dose ◽  
Phase 1 ◽  
Bladder Wall ◽  
Absorbed Dose ◽  
Whole Body ◽  
Time Activity ◽  
Urinary Bladder Wall ◽  
Dose Coefficients ◽  
Pet Scans

Abstract Rationale [11C]-UCB-J is an emerging tool for the noninvasive measurement of synaptic vesicle density in vivo. Here, we report human biodistribution and dosimetry estimates derived from sequential whole-body PET using two versions of the OLINDA dosimetry program. Methods Sequential whole-body PET scans were performed in 3 healthy subjects for 2 h after injection of 254 ± 77 MBq [11C]-UCB-J. Volumes of interest were drawn over relevant source organs to generate time-activity curves and calculate time-integrated activity coefficients, with effective dose coefficients calculated using OLINDA 2.1 and compared to values derived from OLINDA 1.1 and those recently reported in the literature. Results [11C]-UCB-J administration was safe and showed mixed renal and hepatobiliary clearance, with largest organ absorbed dose coefficients for the urinary bladder wall and small intestine (21.7 and 23.5 μGy/MBq, respectively). The average (±SD) effective dose coefficient was 5.4 ± 0.7 and 5.1 ± 0.8 μSv/MBq for OLINDA versions 1.1 and 2.1 respectively. Doses were lower than previously reported in the literature using either software version. Conclusions A single IV administration of 370 MBq [11C]-UCB-J corresponds to an effective dose of less than 2.0 mSv, enabling multiple PET examinations to be carried out in the same subject. Trial registration EudraCT number: 2016-001190-32. Registered 16 March 2016, no URL available for phase 1 trials.

scholarly journals Biodistribution and Radiation Dosimetric Analysis of [68Ga]Ga-RM2: A Potent GRPR Antagonist in Prostate Carcinoma Patients

Radiation ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 33-44
Author(s):  
Matthias Haendeler ◽  
Ambreen Khawar ◽  
Hojjat Ahmadzadehfar ◽  
Stefan Kürpig ◽  
Michael Meisenheimer ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Prostate Carcinoma ◽  
Bladder Wall ◽  
Absorbed Dose ◽  
Stomach Wall ◽  
Physiological Uptake ◽  
Absorbed Doses ◽  
Pet Tracer ◽  
Red Marrow ◽  
Positron Emission

[68Ga]Ga-RM2 is a promising innovative positron emission tomography (PET) tracer for patients with primary or metastatic prostate carcinoma. This study aims to analyze the biodistribution and radiation dosimetry of [68Ga]Ga-RM2 in five prostate cancer patients. The percentages of injected activity in the source organs and blood samples were determined. Bone marrow residence time was calculated using an indirect blood-based method. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) was used to determine residence times, organ absorbed and effective doses. Physiological uptake was seen in kidneys, urinary bladder, pancreas, stomach, spleen and liver. Blood clearance was fast and followed by rapid clearance of activity from kidneys resulting in high activity concentrations in the urinary bladder. The urinary bladder wall was the most irradiated organ with highest mean organ absorbed dose (0.470 mSv/MBq) followed by pancreas (0.124 mSv/MBq), stomach wall (0.063 mSv/MBq), kidneys (0.049 mSv/MBq) and red marrow (0.010 mSv/MBq). The effective dose was found to be 0.038 mSv/MBq. Organ absorbed doses were found to be comparable to other gallium-68 labelled GRPR antagonists and lower than [68Ga]Ga-PSMA with the exception of the urinary bladder, pancreas and stomach wall. Remarkable interindividual differences were observed for the organ absorbed doses. Therefore, [68Ga]Ga-RM2 is a safe diagnostic agent with a significantly lower kidney dose but higher pancreas and urinary bladder doses as compared to [68Ga]Ga-PSMA.

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.

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