Dataset Information

⁶⁸Ga-DOTA-DiPSMA PET/CT Imaging: Biodistribution, Dosimetry, and Preliminary Application in Prostate Cancer.

ABSTRACT: Purpose: This prospective trial aimed to evaluate the safety, dosimetry, and biodistribution of a novel theranostic probe ⁶⁸Ga-DOTA-DiPSMA. Also, we have performed the first preliminary application with ⁶⁸Ga-DOTA-DiPSMA in prostate cancer (PCa) patients. Methods: Five healthy volunteers and ten PCa patients were injected with an intravenous bolus of ⁶⁸Ga-DOTA-DiPSMA. They received serial whole-body PET scans from the time of injection up to 60 min post-injection, with a second PET/CT scanning at 120 min post-injection. In PCa patients, low-dose CT scan and whole-body PET were performed with 2 min per bed position in 40 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake and tumor lesion uptake were measured. A lesion-by-lesion analysis was performed. Results: ⁶⁸Ga-DOTA-DiPSMA administration was safe and well-tolerated. The kidneys received the highest absorbed dose (114.46 ± 29.28 μSv/MBq), followed by the urinary bladder wall (100.82 ± 46.22 μSv/MBq) in accordance with the expected Prostate-Specific Membrane Antigen (PSMA) renal excretion of the tracer. The mean effective dose was 19.46 ± 1.73 μSv/MBq. The SUV_max of ⁶⁸Ga-DOTA-DiPSMA PET/CT for PCa lesions, bone metastases, and lymph node metastases was 4.41 ± 2.72, 2.95 ± 1.11, and 3.26 ± 1.20, respectively. Conclusion: Injection of ⁶⁸Ga-DOTA-DiPSMA is safe and associated with low absorbed and effective doses. ⁶⁸Ga-DOTA-DiPSMA shows favorable kinetics and imaging characteristics in patients who warrant further head-to-head comparison to validate ⁶⁸Ga-DOTA-DiPSMA as an alternative for gallium-68-labeled PSMA clinical PET. Low nonspecific uptake in normal organs of ⁶⁸Ga-DOTA-DiPSMA indicates potential radioligand therapy (RLT) application when labeled with ¹⁷⁷Lu, ⁹⁰Y, or ²²⁵Ac.

SUBMITTER: Zhang J

PROVIDER: S-EPMC8831372 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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68Ga-DOTA-DiPSMA PET/CT Imaging: Biodistribution, Dosimetry, and Preliminary Application in Prostate Cancer.

Zhang Jiaying J Lin Zefang Z Zhang Xiaojun X Lin Rong R Cui Mengchao M Miao Weibing W Yao Shaobo S

Frontiers in bioengineering and biotechnology 20220128

Purpose: This prospective trial aimed to evaluate the safety, dosimetry, and biodistribution of a novel theranostic probe 68Ga-DOTA-DiPSMA. Also, we have performed the first preliminary application with 68Ga-DOTA-DiPSMA in prostate cancer (PCa) patients. Methods: Five healthy volunteers and ten PCa patients were injected with an intravenous bolus of 68Ga-DOTA-DiPSMA. They received serial whole-body PET scans from the time of injection up to 60 min p ...[more]

PMID: 35155411

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Project description:PurposeIn the characterization of severe lung diseases, early detection of specific inflammatory cells could help to monitor patients' response to therapy and increase chances of survival. Macrophages contribute to regulating the resolution and termination of inflammation and have increasingly been of interest for targeted therapies. [68Ga]Ga-DOTA-TATE is an established clinical radiopharmaceutical targeting somatostatin receptor subtype 2 (SSTR 2). Since activated macrophages (M1) overexpress SSTR 2, the aim of this study was to investigate the applicability of [68Ga]Ga-DOTA-TATE for positron emission tomography (PET) imaging of M1 macrophages in pulmonary inflammation.MethodsInflammation in the pig lungs was induced by warm saline lavage followed by injurious ventilation in farm pigs (n = 7). Healthy pigs (n = 3) were used as control. A 60-min dynamic PET scan over the lungs was performed after [68Ga]Ga-DOTA-TATE injection and [18F]FDG scan was executed afterward for comparison. The uptake of both tracers was assessed as mean standardized uptake values (SUVmean) 30-60-min post-injection. The PET scans were followed by computed tomography (CT) scans, and the Hounsfield units (HU) were quantified of the coronal segments. Basal and apical segments of the lungs were harvested for histology staining. A rat lung inflammation model was also studied for tracer specificity using lipopolysaccharides (LPS) by oropharyngeal aspiration. Organ biodistribution, ex vivo autoradiography (ARG) and histology samples were conducted on LPS treated, octreotide induced blocking and control healthy rats.ResultsThe accumulation of [68Ga]Ga-DOTA-TATE on pig lavage model was prominent in the more severely injured dorsal segments of the lungs (SUVmean = 0.91 ± 0.56), compared with control animals (SUVmean = 0.27 ± 0.16, p < 0.05). The tracer uptake corresponded to the damaged areas assessed by CT and histology and were in line with HU quantification. The [68Ga]Ga-DOTA-TATE uptake in LPS treated rat lungs could be blocked and was significantly higher compared with control group.ConclusionThe feasibility of the noninvasive assessment of tissue macrophages using [68Ga]Ga-DOTA-TATE/PET was demonstrated in both porcine and rat lung inflammation models. [68Ga]Ga-DOTA-TATE has a great potential to be used to study the role and presence of macrophages in humans in fight against severe lung diseases.

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:PurposeThere is a lack of validated imaging biomarkers for prediction of response to peptide receptor radionuclide therapy (PRRT). The primary objective was to evaluate if tumour burden at baseline PET/CT could predict treatment outcomes to PRRT with [177Lu]Lu-DOTA-TATE. Secondary objectives were to evaluate if there was a correlation between tumour burden and mean tumour absorbed dose (AD) during first cycle, and if mean tumour AD or the relative change of tumour burden at first follow-up PET/CT could predict progression free survival (PFS) or overall survival (OS).MethodsPatients with gastroenteropancreatic neuroendocrine tumour (GEP-NET) treated with [177Lu]Lu-DOTA-TATE PRRT were retrospectively included. Tumour burden was quantified from [68 Ga]Ga-DOTA-TOC/TATE PET/CT-images at baseline and first follow-up and expressed as; whole-body somatostatin receptor expressing tumour volume (SRETVwb), total lesion somatostatin receptor expression (TLSREwb), largest tumour lesion diameter and highest SUVmax. The relative change of tumour burden was evaluated in three categories. Mean tumour AD was estimated from the first cycle of PRRT. PFS was defined as time from start of PRRT to radiological or clinical progression. OS was evaluated as time to death. Kaplan Meier survival curves and log-rank test were used to compare PFS and OS between different groups.ResultsThirty-one patients had a baseline PET/CT < 6 months before treatment and 25 had a follow-up examination. Median tumour burden was 132 ml (IQR 61-302) at baseline and 71 ml (IQR 36-278) at follow-up. Twenty-two patients had disease progression (median time to progression 17.2 months) and 9 patients had no disease progression (median follow-up 28.7 months). SRETVwb dichotomized by the median at baseline was not associated with longer PFS (p = 0.861) or OS (p = 0.937). Neither TLSREwb, largest tumour lesion or SUVmax showed significant predictive value. There was a moderately strong correlation, however, between SUVmax and mean tumour AD r = 0.705, p < 0.001, but no significant correlation between SRETVwb nor TLSREwb and mean tumour AD. An increase of SRETVwb, TLSREwb or largest tumour lesion at first follow-up PET/CT was significantly correlated with shorter PFS/OS.ConclusionTumour burden at baseline showed no predictive value of PFS/OS after PRRT in this small retrospective study. An increase of tumour burden was predictive of worse outcome.

Project description:PurposeWe aimed to compare the diagnostic performance and biodistribution of two similar PET agents, [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11, in the same group of primary prostate cancer (PCa) patients.MethodsFifty patients with untreated, histologically confirmed PCa by needle biopsy were enrolled. Each patient underwent [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11 PET/CT within a week. In addition to visual analysis, the standardized uptake value (SUV) was measured for semiquantitative comparison and correlation analysis.Results[68Ga]Ga-P16-093 PET/CT detected more positive tumors than [68Ga]Ga-PSMA-11 PET/CT (202 vs. 190, P = 0.002), both for intraprostatic lesions (48 vs. 41, P = 0.016) and metastatic lesions (154 vs. 149, P = 0.125), especially for intraprostatic lesions in low- and intermediate-risk PCa patients (21/23 vs. 15/23, P = 0.031). Furthermore, [68Ga]Ga-P16-093 PET/CT exhibited a significantly higher SUVmax for most matched tumors (13.7 ± 10.2 vs. 11.4 ± 8.3, P < 0.001). For normal organs, [68Ga]Ga-P16-093 PET/CT showed significantly lower activity in the kidney (SUVmean: 20.1 ± 6.1 vs. 29.3 ± 9.1, P < 0.001) and urinary bladder (SUVmean: 6.5 ± 7.1 vs. 20.9 ± 17.4, P < 0.001), but displayed a higher uptake in the parotid gland (SUVmean: 8.7 ± 2.6 vs. 7.6 ± 2.1, P < 0.001), liver (SUVmean: 7.0 ± 1.9 vs. 3.7 ± 1.3, P < 0.001), and spleen (SUVmean: 8.2 ± 3.0 vs. 5.2 ± 2.2, P < 0.001) than [68Ga]Ga-PSMA-11 PET/CT.Conclusion[68Ga]Ga-P16-093 PET/CT demonstrated higher tumor uptake and better tumor detectability than [68Ga]Ga-PSMA-11 PET/CT, especially in low- and intermediate-risk PCa patients, which indicated that [68Ga]Ga-P16-093 may serve as an alternative agent for detection of PCa.Trial registration68Ga-P16-093 and 68Ga-PSMA-11 PET/CT Imaging in the Same Group of Primary Prostate Cancer Patients (NCT05324332, Registered 12 April 2022, retrospectively registered). URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT05324332 .

Dataset Information

⁶⁸Ga-DOTA-DiPSMA PET/CT Imaging: Biodistribution, Dosimetry, and Preliminary Application in Prostate Cancer.

Publications

<sup>68</sup>Ga-DOTA-DiPSMA PET/CT Imaging: Biodistribution, Dosimetry, and Preliminary Application in Prostate Cancer.

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