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Article ; Online: Scale down and optimized automated production of [68Ga]68Ga-DOTA-ECL1i PET tracer targeting CCR2 expression.

Migliari, Silvia / Scarlattei, Maura / Baldari, Giorgio / Ruffini, Livia

EJNMMI radiopharmacy and chemistry

2023 Volume 8, Issue 1, Page(s) 3

Abstract: Background: Recently it has been identified a short peptide that showed allosteric antagonism against C-C motif chemokine receptor 2 (CCR2) expressed on inflammatory monocyte and macrophages. A 7-D-amino acid peptidic CCR2 inhibitor called extracellular ...

Abstract	Background: Recently it has been identified a short peptide that showed allosteric antagonism against C-C motif chemokine receptor 2 (CCR2) expressed on inflammatory monocyte and macrophages. A 7-D-amino acid peptidic CCR2 inhibitor called extracellular loop 1 inverso (ECL1i), d(LGTFLKC) has been identified and labeled to obtain a new probe for positron emission tomography in pulmonary fibrosis, heart injury, abdominal aortic aneurysm inflammation, atherosclerosis, head and neck cancer. Our goal was to develop, optimize and validate an automated synthesis method for [68Ga]68Ga-DOTA-ECL1i to make it available for a broader community. The synthesis of [68Ga]68Ga-DOTA-ECL1i was done using the Scintomics GRP Results: Best results were yielded with 20 μg DOTA-ECL1i and then the process validation was carried out by producing three different batches on three different days obtaining an optimal radiochemical yield (66.69%) as well as radiochemical purity (100%) and molar activity (45.41 GBq/µmol). Conclusions: [68Ga]68Ga-DOTA-ECL1i was successfully synthesized and it is, thus, available for multi-dose application in clinical settings.
Language	English
Publishing date	2023-02-02
Publishing country	England
Document type	Journal Article
ISSN	2365-421X
ISSN (online)	2365-421X
DOI	10.1186/s41181-023-00188-1
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Article ; Online: Scale down and optimized automated production of [68Ga]68Ga-DOTA-ECL1i PET tracer targeting CCR2 expression

Silvia Migliari / Maura Scarlattei / Giorgio Baldari / Livia Ruffini

EJNMMI Radiopharmacy and Chemistry, Vol 8, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract Background Recently it has been identified a short peptide that showed allosteric antagonism against C–C motif chemokine receptor 2 (CCR2) expressed on inflammatory monocyte and macrophages. A 7-d-amino acid peptidic CCR2 inhibitor called ... ...

Abstract	Abstract Background Recently it has been identified a short peptide that showed allosteric antagonism against C–C motif chemokine receptor 2 (CCR2) expressed on inflammatory monocyte and macrophages. A 7-d-amino acid peptidic CCR2 inhibitor called extracellular loop 1 inverso (ECL1i), d(LGTFLKC) has been identified and labeled to obtain a new probe for positron emission tomography in pulmonary fibrosis, heart injury, abdominal aortic aneurysm inflammation, atherosclerosis, head and neck cancer. Our goal was to develop, optimize and validate an automated synthesis method for [68Ga]68Ga-DOTA-ECL1i to make it available for a broader community. The synthesis of [68Ga]68Ga-DOTA-ECL1i was done using the Scintomics GRP® module with the already estabilished synthesis template for [68Ga]68Ga-DOTATOC/[68Ga]68Ga-PSMA. The radiopharmaceutical production was optimized scaling down the amount of DOTA-ECL1i (from 50 to 10 μg), evaluating synthesis efficiency and relevant quality control parameters in accordance with the European Pharmacopeia. Results Best results were yielded with 20 μg DOTA-ECL1i and then the process validation was carried out by producing three different batches on three different days obtaining an optimal radiochemical yield (66.69%) as well as radiochemical purity (100%) and molar activity (45.41 GBq/µmol). Conclusions [68Ga]68Ga-DOTA-ECL1i was successfully synthesized and it is, thus, available for multi-dose application in clinical settings.
Keywords	[68Ga]68Ga-radiopharmaceuticals ; [68Ga]68Ga-DOTA-ECL1i ; CC chemokine receptor type 2 (CCR2) ; PET imaging ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Therapeutics. Pharmacology ; RM1-950
Subject code	540
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
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Article: Validation of the HPLC Analytical Method for the Determination of Chemical and Radiochemical Purity of Ga-68-DOTATATE.

Sammartano, Antonino / Migliari, Silvia / Serreli, Giulio / Scarlattei, Maura / Baldari, Giorgio / Ruffini, Livia

Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India

2023 Volume 38, Issue 1, Page(s) 1–7

Abstract: Purpose of the study: Ga-68-DOTA-peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumors imaging using positron emission tomography (PET). A new selective and sensitive high-pressure liquid chromatography ...

Abstract	Purpose of the study: Ga-68-DOTA-peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumors imaging using positron emission tomography (PET). A new selective and sensitive high-pressure liquid chromatography (HPLC) method was developed for determining chemical and radiochemical purity of Ga-68-DOTATATE (PET) tracer. The identification of peaks was achieved on a symmetry C18 column 3 μm 120Å (3.0 mm × 150 mm spherical particles) using (A) water + 0.1% trifluoroacetic acid (TFA) and (B) acetonitrile + 0.1% TFA, as the mobile phases at a flow rate of 0.600 mL/min and monitored at 220 nm. The run time was 16 min. Materials and methods: The method was validated to fulfill International Conference on Harmonization requirements and EDQM guidelines, and it included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision. Results: The calibration curve was linear over the concentration range from 0.5 to 3 μg/ml, with a correlation coefficient (r2) equal to 0.999, average coefficient of variation (CV%) 2%, and average bias% did not deviate more than 5% for all concentrations. The LOD and LOQ for DOTATATE were 0.5 and 0.1 μg/mL, respectively. The method was considered precise, obtaining coefficients of variation between 0.22% and 0.52% for intraday and 0.20% and 0.61% for interday precision. Accuracy of method was confirmed with average bias% that did not deviate more than 5% for all concentrations. Conclusion: All results were acceptable and this confirmed that the method is suitable for its intended use in routine quality control of Ga-68-DOTATATE to guarantee the high quality of the finished product before release.
Language	English
Publishing date	2023-02-24
Publishing country	India
Document type	Journal Article
ZDB-ID	2181722-4
ISSN	0974-0244 ; 0972-3919
ISSN (online)	0974-0244
ISSN	0972-3919
DOI	10.4103/ijnm.ijnm_11_22
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Article ; Online: A Specific HPLC Method to Determine Residual HEPES in [

Migliari, Silvia / Scarlattei, Maura / Baldari, Giorgio / Silva, Claudia / Ruffini, Livia

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 14

Abstract: Background: Nowadays, in Nuclear Medicine, clinically applied radiopharmaceuticals must meet quality release criteria such as high radiochemical purity and radiochemical yield. Many radiopharmaceuticals do not have marketing authorization and have no ... ...

Abstract	Background: Nowadays, in Nuclear Medicine, clinically applied radiopharmaceuticals must meet quality release criteria such as high radiochemical purity and radiochemical yield. Many radiopharmaceuticals do not have marketing authorization and have no dedicated monograph within European Pharmacopeia (Ph. Eur.); therefore, general monographs on quality controls (QCs) have to be applied for clinical application. These criteria require standardization and validation in labeling and preparation, including quality controls measurements, according to well defined standard operation procedures. However, QC measurements are often based on detection techniques that are specific to a certain chromatographic system. Several radiosyntheses of [68Ga]Ga-radiopharmaceuticals are more efficient and robust when they are performed with 2-[4-(2-hydroxyethyl)piperazin-1-yl] ethanesulfonic acid (HEPES) buffer, which is considered as an impurity to be assessed in the QC procedure, prior to clinical use. Thus, Ph. Eur. has introduced a thin-layer chromatography (TLC) method to quantify the HEPES amount that is present in [68Ga]Ga-radiopharmaceuticals. However, this is only qualitative and has proven to be unreliable. Here we develop and validate a new high-performance liquid chromatography (UV-Radio-HPLC) method to quantify the residual amount of HEPES in 68Ga-based radiopharmaceuticals. Method: To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document that was adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. A range of concentrations of HEPES (100, 80, 60, 40, 20, 10, 5, 3 μg/mL) were analyzed. Moreover, to test the validity and pertinence of our new HPLC method, we analyzed samples of [68Ga]Ga-DOTATOC; [68Ga]Ga-PSMA; [68Ga]Ga-DOTATATE; [68Ga]Ga-Pentixafor; and [68Ga]Ga-NODAGA-Exendin-4 from different batches that were prepared for clinical use. Results: In the assessed samples, HEPES could not be detected by the TLC method that was described in Ph. Eur. within 4 min incubation in an iodine-saturated chamber. Our developed HPLC method showed excellent linearity between 3 and 100 μg/mL for HEPES, with a correlation coefficient (R2) for calibration curves that was equal to 0.999, coefficients of variation (CV%) < 2%, and percent deviation value of bias from 100% to 5%, in accordance with acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed and the limit-of-quantification (LOQ) was 3 μg/mL, confirming the high sensitivity of the method. The amount of HEPES that was detected with our developed HPLC method in the tested [68Ga]Ga-radiopharmaceuticals resulted well below the Ph. Eur. limit, especially for [68Ga]Ga-NODAGA-Exendin-4. Conclusions: The TLC method that is described in Ph. Eur. to assess residual HEPES in [68Ga]-based radiopharmaceuticals may not be sufficiently sensitive and thus unsuitable for QC release. Our new HPLC method was sensitive, quantitative, reproducible, and rapid for QCs, allowing us to exactly determine the residual HEPES amount in [68Ga]Ga-radiopharmaceuticals for safe patient administration.
MeSH term(s)	Chromatography, High Pressure Liquid ; Exenatide ; Gallium Radioisotopes/chemistry ; HEPES ; Positron-Emission Tomography ; Radionuclide Imaging ; Radiopharmaceuticals/chemistry
Chemical Substances	Gallium Radioisotopes ; Radiopharmaceuticals ; copper dotatate CU-64 ; Exenatide (9P1872D4OL) ; HEPES (RWW266YE9I)
Language	English
Publishing date	2022-07-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27144477
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Article ; Online: Relationship between comprehensive geriatric assessment and amyloid PET in older persons with MCI.

Lauretani, Fulvio / Ruffini, Livia / Scarlattei, Maura / Maggio, Marcello

BMC geriatrics

2020 Volume 20, Issue 1, Page(s) 337

Abstract: Background: The association between amyloid deposition and cognitive, behavioral and physical performance in mild cognitive impairment (MCI) due to Alzheimer's disease (AD) has been poorly investigated, especially in older persons.: Methods: We ... ...

Abstract	Background: The association between amyloid deposition and cognitive, behavioral and physical performance in mild cognitive impairment (MCI) due to Alzheimer's disease (AD) has been poorly investigated, especially in older persons. Methods: We studied the in vivo correlation between the amyloid deposition at Positron Emission Tomography (amyloid-PET) and the presence of memory loss, reduced executive function, neuropsychiatric symptoms and physical performance in older persons with MCI. Amyloid-PET was performed with 18F-flutemetamol and quantitatively analyzed. Results: We evaluated 48 subjects, 21 men and 27 women. We performed in each patient a comprehensive geriatric assessment (CGA) including Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Activity Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Neuropsychiatric inventory (NPI) questionnaire, 15 Geriatric Depression Scale (GDS), Short Physical Performance Battery (SPPB) and Hand Grip strength. Then, each patient underwent amyloid-PET. Mean age of the enrolled subjects was 74.6 ± 7.8 years. All of these subjects showed preserved cognitive function at MMSE > 24, while 29 of 48 subjects (61.0%) had altered CDT. Mean NPI score was 6.9 ± 5.9. The mean value of SPPB score was 9.0 ± 2.6, while the average muscle strength of the upper extremities measured by hand grip was 25.6 ± 7.7 Kg. CT/MRI images showed cortical atrophic changes in 26 of the 48 examined subjects (54.0%), while cerebrovascular modifications were present in 31 subjects (64.5%). Pathological burden of amyloid deposits was detected in 25 of 48 (52.0%) patients with a mean value of global z-score of 2.8 (subjects defined as MCI due to AD). After stratifying subjects in subclasses of clinical alterations, more probability of pathological amyloid deposition was found in subjects with impaired CDT and higher NPI score (O.R. = 3.45 [1.01-11.2], p = 0.04), with both impaired CDT and low physical performance (O.R. = 5.80 [1.04-32.2], p = 0.04), with altered CDT and high NPI score (O.R. = 7.98 [1.38-46.0], p = 0.02), and finally in those subjects with altered CDT, high NPI and low physical performance (O.R. = 5.80 [1.05-32.2], p = 0.04). Conclusion: Our findings support the recent hypothesis that amyloid deposition could be associated with multiple cerebral dysfunction, mainly affecting executive, behavioral and motor abilities.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease ; Cognitive Dysfunction/diagnostic imaging ; Female ; Geriatric Assessment ; Hand Strength ; Humans ; Male ; Positron-Emission Tomography
Language	English
Publishing date	2020-09-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-020-01746-x
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Article: Validation of Quality Control Parameters of Cassette-Based Gallium-68-DOTA-Tyr3-Octreotate Synthesis.

Sammartano, Antonino / Migliari, Silvia / Scarlattei, Maura / Baldari, Giorgio / Ruffini, Livia

Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India

2020 Volume 35, Issue 4, Page(s) 291–298

Abstract: Purpose of the study: Gallium (Ga)-68-DOTA peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumor imaging using positron emission tomography. However, at the moment, a specific monograph in the European ... ...

Abstract	Purpose of the study: Gallium (Ga)-68-DOTA peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumor imaging using positron emission tomography. However, at the moment, a specific monograph in the European Pharmacopoeia (Ph. Eur.) does exist only for Ga-68-edotreotide (DOTATOC) injection. Here, we report on the validation process of Ga-68-DOTA-Tyr3-octreotate (DOTATATE) cassette-based production and quality control (QC). Materials and methods: Preparation of Ga-68-DOTATATE was performed according to the current European Union-good manufacturing practices, the current good radiopharmacy practice, the Ph. Eur., and the guidelines on validation of analytical methods for radiopharmaceuticals. Process was validated via three consecutive production runs to ensure that the methods are reproducible and reliable in routine use. The QC tests for Ga-68-DOTATATE were radiochemical purity (RCP - high-pressure liquid chromatography [HPLC]), radiochemical impurities Results: Radiolabeling procedure of Ga-68-DOTATATE fits all the applicable Ph. Eur. specifications. RCP measured via ITLC was >99% in the three validation batches. HPLC-measured RCP resulted 99.45%, 99.78%, and 99.75%. Germanium-breakthrough was far below the recommended level established in the Ph. Eur. Ga-68-DOTATOC injection (#2482). Residual ethanol tested with GC was less than 10%. All the batches were tested for endotoxin content, which always resulted lower than 17.5 EU/ml. All preparations passed the sterility tests. pH of the final product was 7 in all samples. Conclusion: Ga-68-DOTATATE fulfilled all the pre-set QCs and release criteria in the batches considered for this validation study. The results demonstrated a batch-to-batch reproducibility, ensuring that synthesis process leads to the expected final product in terms of yield, quality, reliability, safety, and efficacy.
Language	English
Publishing date	2020-10-21
Publishing country	India
Document type	Journal Article
ZDB-ID	2181722-4
ISSN	0974-0244 ; 0972-3919
ISSN (online)	0974-0244
ISSN	0972-3919
DOI	10.4103/ijnm.IJNM_66_20
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Article ; Online: Synthesis, validation and quality controls of [68Ga]-DOTA-Pentixafor for PET imaging of chemokine receptor CXCR4 expression.

Sammartano, Antonino / Migliari, Silvia / Scarlattei, Maura / Baldari, Giorgio / Ruffini, Livia

Acta bio-medica : Atenei Parmensis

2020 Volume 91, Issue 4, Page(s) e2020097

Abstract: Background: Chemokine receptor-4 (CXCR4) is involved in tumor growth and progression in several types of human cancer. Recently, [68Ga]-DOTA-Pentixafor has been assessed as an excellent imaging probe targeting CXCR4-expression using positron emission ... ...

Abstract	Background: Chemokine receptor-4 (CXCR4) is involved in tumor growth and progression in several types of human cancer. Recently, [68Ga]-DOTA-Pentixafor has been assessed as an excellent imaging probe targeting CXCR4-expression using positron emission tomography (PET). Here we report on the entire production cycle of [68Ga]-DOTA-Pentixafor, including quality control development and process validation. Methods: Synthesis of [68Ga]-DOTA-Pentixafor was validated via three independent and consecutive production runs using an automated synthesis system. All validation runs must pass the pre-set quality control (QC) limits. Validation was performed for established QC tests to ensure that methods were reproducible and reliable in routine use. Germanium-68 breakthrough was determined for each sample. Production yield was calculated for each synthesis to assess the performance and efficiency of the radiolabeling process. The quality of the final product was determined by ITLC and HPLC methods after each synthesis. Results: The average ITLC-measured radiochemical purity was above 98.5% and HPLC-measured radiochemical purity was 99.86%, 99,83% and 100% in the three validation runs. Germanium breakthrough was 4.810-5%, 4.910-5% and 4.710-5% of total activity, far below the recommended level of 0.001%. Residual ethanol resulted 5.22%, 5.58% and 5.32%V/V; spot of HEPES impurity was not more intense than spot of reference solution (200µg/V). Endotoxin level resulted <17.5EU/ml. pH of the final product was 7 in all samples. Conclusion:* [68Ga]-DOTA-Pentixafor fit requirements of the pre-set quality parameters of purity, efficacy and safety in the batches considered for this study and fulfilled all the acceptance criteria for injectable radiopharmaceutical products. The results demonstrated a batch-to-batch reproducibility providing high radiochemical purity.
MeSH term(s)	Coordination Complexes ; Humans ; Peptides, Cyclic ; Positron-Emission Tomography ; Quality Control ; Receptors, CXCR4 ; Reproducibility of Results
Chemical Substances	68Ga-pentixafor ; CXCR4 protein, human ; Coordination Complexes ; Peptides, Cyclic ; Receptors, CXCR4
Language	English
Publishing date	2020-07-06
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2114240-3
ISSN	2531-6745 ; 0392-4203
ISSN (online)	2531-6745
ISSN	0392-4203
DOI	10.23750/abm.v91i4.9106
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Article ; Online: A Rapid and Specific HPLC Method to Determine Chemical and Radiochemical Purity of [

Migliari, Silvia / Sammartano, Antonino / Scarlattei, Maura / Baldari, Giorgio / Silva, Claudia / Ruffini, Livia

Current radiopharmaceuticals

2021 Volume 14, Issue 2, Page(s) 121–130

Abstract: Background: Due to its overexpression in a variety of tumor types, the chemokine receptor 4 (CXCR4) represents a highly relevant diagnostic and therapeutic target in nuclear oncology. Recently, [: Objective: The developed analytical test method was ... ...

Abstract	Background: Due to its overexpression in a variety of tumor types, the chemokine receptor 4 (CXCR4) represents a highly relevant diagnostic and therapeutic target in nuclear oncology. Recently, [ Objective: The developed analytical test method was validated because a specific monograph in the Pharmacopoeia is not available for [68Ga]Ga-DOTA-Pentixafor. Method: A stepwise approach was used based on the quality by design (QbD) concept of the ICH Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of EANM, SNM, IAEA and WHO. Results: The purity and quality of the radiopharmaceutical obtained according to the proposed method were found to be high enough to safely administrate it to patients. Excellent linearity was found between 0.5 and 4 μg/mL, with a correlation coefficient (r Conclusion: This study developed a new rapid and simple HPLC method of analysis for the routine QCs of [
Language	English
Publishing date	2021-01-12
Publishing country	United Arab Emirates
Document type	Journal Article
ISSN	1874-4729
ISSN (online)	1874-4729
DOI	10.2174/1874471013666200929125102
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Article ; Online: Development and Validation of an Analytical HPLC Method to Assess Chemical and Radiochemical Purity of [

Migliari, Silvia / Sammartano, Antonino / Boss, Marti / Gotthardt, Martin / Scarlattei, Maura / Baldari, Giorgio / Silva, Claudia / Bonadonna, Riccardo C / Ruffini, Livia

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 2

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Acetates/analysis ; Acetates/chemistry ; Calibration ; Chromatography, High Pressure Liquid/methods ; Chromatography, Thin Layer ; Exenatide/analysis ; Exenatide/chemistry ; Gallium Radioisotopes/analysis ; Gallium Radioisotopes/chemistry ; Heterocyclic Compounds, 1-Ring/analysis ; Heterocyclic Compounds, 1-Ring/chemistry ; Humans ; Insulinoma/diagnosis ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/analysis ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/chemistry ; Ultraviolet Rays
Chemical Substances	1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane ; Acetates ; Gallium Radioisotopes ; Heterocyclic Compounds, 1-Ring ; Radiopharmaceuticals ; Gallium-68 (98B30EPP5S) ; Exenatide (9P1872D4OL)
Language	English
Publishing date	2022-01-15
Publishing country	Switzerland
Document type	Journal Article ; Validation Study
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27020543
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Article: High Prognostic Value of

Gasparro, Donatello / Scarlattei, Maura / Silini, Enrico Maria / Migliari, Silvia / Baldari, Giorgio / Cervati, Veronica / Graziani, Tiziano / Campanini, Nicoletta / Maestroni, Umberto / Ruffini, Livia

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 19

Abstract: In oligo-metastatic renal cell carcinoma (RCC), neither computed tomography (CT) nor bone scan is sensitive enough to detect small tumor deposits hampering early treatment and potential cure. Prostate-specific membrane antigen (PSMA) is a transmembrane ... ...

Abstract	In oligo-metastatic renal cell carcinoma (RCC), neither computed tomography (CT) nor bone scan is sensitive enough to detect small tumor deposits hampering early treatment and potential cure. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in the neo-vasculature of numerous malignant neoplasms, including RCC, that can be targeted by positron emission tomography (PET) using PSMA-targeting radioligands. Our aim was to investigate whether PSMA-expression patterns of renal cancer in the primary tumor or metastatic lesions on immunohistochemistry (IHC) are associated with PET/CT findings using [
Language	English
Publishing date	2023-09-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13193082
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