Dataset Information

Biodistribution, dosimetry, and temporal signal-to-noise ratio analyses of normal and cancer uptake of [⁶⁸Ga]Ga-P15-041, a gallium-68 labeled bisphosphonate, from first-in-human studies.

ABSTRACT:

Introduction

[⁶⁸Ga]Ga-P15-041 ([⁶⁸Ga]Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer that can be generator-produced. We undertook a Phase 0/I clinical trial to assess its potential for imaging bone metastases in prostate cancer including assessment of radiotracer biodistribution and dosimetry.

Methods

Subjects with prostate cancer and known or suspected osseous metastatic disease were enrolled into one of two arms: dosimetry or dynamic. Dosimetry was performed with 6 whole body PET acquisitions and urine collection spanning 3 h; normal organ dosimetry was calculated using OLINDA/EXM. Dynamic imaging included a 60 min acquisition over a site of known or suspected disease followed by two whole body scans. Bootstrapping and subsampling of the acquired list-mode data were conducted to recommend image acquisition parameters for future clinical trials.

Results

Up to 233 MBq (6.3 mCi) of [⁶⁸Ga]Ga-P15-041 was injected into 12 enrolled volunteers, 8 in dosimetry and 4 in dynamic cohorts. Radiotracer accumulated in known bone lesions and cleared rapidly from blood and soft tissue. The highest individual organ dose was 0.135 mSv/MBq in the urinary bladder wall. The average effective dose was 0.0173 ± 0.0036 mSv/MBq. An average injected activity of 166.5 MBq (4.5 mCi) resulted in absorbed dose estimates of 22.5 mSv to the urinary bladder wall, 8.2 mSv to the kidneys, and an effective dose of 2.9 mSv. Lesion signal to noise ratios on images generated from subsampled data were significantly higher for injected activities above 74 MBq (2 mCi) and were also significantly higher for imaging at 90 min than at 180 min post-injection.

Conclusions

Dosimetry estimates are acceptable and [⁶⁸Ga]Ga-P15-041 uptake characteristics in patients with confirmed bone metastases support its continued development.

Advances in knowledge and implications for patient care

Use of [⁶⁸Ga]Ga-P15-041 would not require cyclotron infrastructure for manufacturing and distribution, allowing for improved patient access to a promising PET bone imaging agent.

SUBMITTER: Doot RK

PROVIDER: S-EPMC7311273 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objectives68Ga-P15-041 (68Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer, which can be readily prepared by using a simple kit formulation and an in-house 68Ga/68Ge generator. The aim of this study is to assess the potential human application of 68Ga-P15-041 for clinical PET/CT imaging and to compare its efficacy to detect bone metastases of different cancers with 99mTc-MDP whole-body bone scintigraphy (WBBS).MethodsInitial kinetic study using Patlak analysis and parametric maps were performed in five histopathologically proven cancer patients (three males, two females) using 68Ga-P15-041 PET/CT scan only. Another group of 51 histopathologically proven cancer patients (22 males, 29 females) underwent both 99mTc-MDP WBBS and 68Ga-P15-041 PET/CT scans within a week, sequentially. Using either pathology examination or follow-up CT or MRI scans as the gold standard, the diagnostic efficacy and receiver operating characteristic curve (ROC) of the two methods in identifying bone metastases were compared (p <0.05, statistically significant).ResultsFifty-one patients were imaged, and 174 bone metastatic sites were identified. 68Ga-P15-041 PET/CT and 99mTc-MDP WBBS detected 162 and 81 metastases, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 68Ga-P15-041 PET/CT and 99mTc-MDP WBBS were 93.1% vs 81.8%, 89.8% vs 90.7%, 77.5% vs 69.2%, 97.2% vs 93.4% and 90.7% vs 88.4%, respectively. Our results showed that the mean of SUVmax was significantly higher in metastases than that in benign lesions, 15.1 ± 6.9 vs. 5.6 ± 1.3 (P <0.001). Using SUVmax = 7.6 as the cut-off value by PET/CT, it was possible to predict the occurrence of metastases (AUC = 0.976; P <0.001; 95% CI: 0.946-0.999). However, it was impossible to distinguish osteoblastic bone metastases from osteolytic bone lesions. Parametric maps based on Patlak analysis provided excellent images and highly valuable quantitative information.Conclusions68Ga-P15-041 PET/CT, offering a rapid bone scan and high contrast images in minutes, is superior to the current method of choice in detecting bone metastases. It is reasonable to suggest that 68Ga-P15-041 PET/CT could become a valuable routine nuclear medicine procedure in providing excellent images for detecting bone metastases in cancer patients. 68Ga-P15-041 could become a valuable addition expanding the collection of 68Ga-based routine nuclear medicine procedures where 18F fluoride is not currently available.

Project description:Targeting cancer-associated fibroblasts (CAFs) has become an attractive goal for diagnostic imaging and therapy because they can constitute as much as 90% of a tumor mass. The serine protease fibroblast activation protein (FAP) is overexpressed selectively in CAFs, drawing interest in FAP as a stromal target. The quinoline-based FAP inhibitor (FAPI) PET tracer 68Ga-FAPI-04 has been previously shown to yield high tumor-to-background ratios (TBRs) in patients with various cancers. Recent developments toward an improved compound for therapeutic application have identified FAPI-46 as a promising agent because of an increased tumor retention time in comparison with FAPI-04. Here, we present a PET biodistribution and radiation dosimetry study of 68Ga-FAPI-46 in cancer patients. Methods: Six patients with different cancers underwent serial 68Ga-FAPI-46 PET/CT scans at 3 time points after radiotracer injection: 10 min, 1 h, and 3 h. The source organs consisted of the kidneys, bladder, liver, heart, spleen, bone marrow, uterus, and remainder of body. OLINDA/EXM software, version 1.1, was used to fit and integrate the kinetic organ activity data to yield total-body and organ time-integrated activity coefficients and residence times and, finally, organ-absorbed doses. SUVs and TBR were generated from the contoured tumor and source-organ volumes. Spheric volumes in muscle and blood pool were also obtained for TBR (tumor SUVmax/organ SUVmean). Results: At all time points, average SUVmax was highest in the liver. Tumor and organ SUVmean decreased over time, whereas TBRs in all organs but the uterus increased. The organs with the highest effective doses were bladder wall (2.41E-03 mSv/MBq), followed by ovaries (1.15E-03 mSv/MBq) and red marrow (8.49E-04 mSv/MBq). The average effective total-body dose was 7.80E-03 mSv/MBq. Conclusion: 68Ga-FAPI-46 PET/CT has a favorable dosimetry profile, with an estimated whole-body dose of 5.3 mSv for an administration of 200 MBq (5.4 mCi) of 68Ga-FAPI-46 (1.56 ± 0.26 mSv from the PET tracer and 3.7 mSv from 1 low-dose CT scan). The biodistribution study showed high TBRs increasing over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications.

Project description:68Ga-NODAGA-LM3 (where LM3 is p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2) and 68Ga-DOTA-LM3 are somatostatin receptor subtype 2 (SSTR2)-specific antagonists used for PET/CT imaging. The purpose of this study was to evaluate the safety, biodistribution, and dosimetry of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 in patients with well-differentiated neuroendocrine tumors. Methods: Patients were equally randomized into 2 arms, with arm A receiving 68Ga-NODAGA-LM3 and arm B receiving 68Ga-DOTA-LM3. Serial PET scans were acquired at 5, 15, 30, 45, 60, and 120 min after 68Ga-NODAGA-LM3 (200 MBq ± 11 MBq/40 μg of total peptide mass) or 68Ga-DOTA-LM3 (172 MBq ± 21 MBq/40 μg of total peptide mass) injection. The biodistribution in normal organs, tumor uptake, and safety were assessed. Radiation dosimetry was calculated using OLINDA/EXM (version 1.0). Results: Sixteen patients, 8 in each arm, were recruited in the study. Both tracers were well tolerated in most patients. Two patients in arm B had nausea (grade 2), and one of them had vomiting (grade 1). The PET images of the other 14 patients were further analyzed. Significantly lower organ uptake was observed in the pituitary, parotids, liver, spleen, pancreas, adrenal, stomach, small intestine, and kidneys with 68Ga-DOTA-LM3 than with 68Ga-NODAGA-LM3. In total, 38 lesions were analyzed, including 18 with 68Ga-NODAGA-LM3 and 20 with 68Ga-DOTA-LM3. Both tracers showed good tumor uptake and retention. With 68Ga-NODAGA-LM3, the tracer accumulation in tumor lesions increased by 138%, from an average SUVmax of 31.3 ± 19.7 at 5 min to 74.6 ± 56.3 at 2 h. With 68Ga-DOTA-LM3, the tumor uptake rapidly reached a high level at 5 min after injection, with an average SUVmax of 36.6 ± 23.6, and continued to increase to 45.3 ± 29.3 until 30 min after injection. The urinary bladder wall was the organ receiving the highest absorbed dose in both arms. The mean effective dose was 0.026 ± 0.003 mSv/MBq for 68Ga-NODAGA-LM3 and 0.025 ± 0.002 mSv/MBq for 68Ga-DOTA-LM3. Conclusion: Both 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 show favorable biodistribution, high tumor uptake, and good tumor retention, resulting in high image contrast. The dosimetric data are comparable to those for other 68Ga-labeled SSTR2 antagonists. Further studies are required to look into the potential antagonistic effects of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3.

Project description:BackgroundProstate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [68Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.MethodsEligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[18F]FDG PET and/or 131I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [68Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[18F]FDG PET CT/MRI for lesion location and relative intensity.ResultsTwelve patients underwent [68Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[18F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[18F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.Conclusions[68Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[18F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.

Project description:Background68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ([68Ga]PSMA-11) has been increasingly used to image prostate cancer using positron emission tomography (PET)/computed tomography (CT) both during diagnosis and treatment planning. It has been shown to be of clinical value for patients both in the primary and secondary stages of prostate cancer. The aim of this study was to determine the effective dose and organ doses from injection of [68Ga]PSMA-11 in a cohort of low-risk prostate cancer patients.MethodsSix low-risk prostate cancer patients were injected with 133-178 MBq [68Ga]PSMA-11 and examined with four PET/CT acquisitions from injection to 255 min post-injection. Urine was collected up to 4 h post-injection, and venous blood samples were drawn at 45 min, 85 min, 175 min, and 245 min post-injection. Kidneys, liver, lungs, spleen, salivary and lacrimal glands, and total body where delineated, and cumulated activities and absorbed organ doses calculated. The software IDAC-Dose 2.1 was used to calculate absorbed organ doses according to the International Commission on Radiological Protection (ICRP) publication 107 using specific absorbed fractions published in ICRP 133 and effective dose according to ICRP Publication 103. We also estimated the absorbed dose to the eye lenses using Monte Carlo methods.Results[68Ga]PSMA-11 was rapidly cleared from the blood and accumulated preferentially in the kidneys and the liver. The substance has a biological half-life in blood of 6.5 min (91%) and 4.4 h (9%). The effective dose was calculated to 0.022 mSv/MBq. The kidneys received approximately 40 mGy after an injection with 160 MBq [68Ga]PSMA-11 while the lacrimal glands obtained an absorbed dose of 0.12 mGy per administered MBq. Regarding the eye lenses, the absorbed dose was low (0.0051 mGy/MBq).ConclusionThe effective dose for [68Ga]PSMA-11 is 0.022 mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.

Dataset Information

Biodistribution, dosimetry, and temporal signal-to-noise ratio analyses of normal and cancer uptake of [⁶⁸Ga]Ga-P15-041, a gallium-68 labeled bisphosphonate, from first-in-human studies.

Introduction

Methods

Results

Conclusions

Advances in knowledge and implications for patient care

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Biodistribution, dosimetry, and temporal signal-to-noise ratio analyses of normal and cancer uptake of [68Ga]Ga-P15-041, a gallium-68 labeled bisphosphonate, from first-in-human studies.

Introduction

Methods

Results

Conclusions

Advances in knowledge and implications for patient care

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Biodistribution, dosimetry, and temporal signal-to-noise ratio analyses of normal and cancer uptake of [⁶⁸Ga]Ga-P15-041, a gallium-68 labeled bisphosphonate, from first-in-human studies.