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World Journal of Gastroenterology May 2022Theranostics is the highly targeted molecular imaging and therapy of tumors. Targeted peptide receptor radionuclide therapy has taken the lead in demonstrating the... (Review)
Review
Theranostics is the highly targeted molecular imaging and therapy of tumors. Targeted peptide receptor radionuclide therapy has taken the lead in demonstrating the safety and effectiveness of this molecular approach to treating cancers. Metastatic, well-differentiated gastroenteropancreatic neuroendocrine tumors may be most effectively imaged and treated with DOTATATE ligands. We review the current practice, safety, advantages, and limitations of DOTATATE based theranostics. Finally, we briefly describe the exciting new areas of development and future directions of gastroenteropancreatic neuroendocrine tumor theranostics.
Topics: Gallium Radioisotopes; Humans; Intestinal Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Peptide; Stomach Neoplasms
PubMed: 35633909
DOI: 10.3748/wjg.v28.i17.1768 -
Future Oncology (London, England) Sep 2021
Topics: Gallium Isotopes; Gallium Radioisotopes; Humans; Male; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms
PubMed: 34251277
DOI: 10.2217/fon-2021-0629 -
Journal of Nuclear Medicine : Official... Mar 1980
Review
Topics: Animals; Bacterial Infections; Gallium Radioisotopes; Humans; Infections; Lactoferrin; Leukocytes; Neoplasms; Radionuclide Imaging
PubMed: 6988551
DOI: No ID Found -
Minerva Endocrinologica Jun 2008
Topics: Endocrine System Diseases; Endocrinology; Fluorodeoxyglucose F18; Gallium Radioisotopes; Humans; Nuclear Medicine; Positron-Emission Tomography; Radiopharmaceuticals; Thyroid Diseases; Tomography, Emission-Computed, Single-Photon
PubMed: 18388855
DOI: No ID Found -
Theranostics 2022: Radiolabeled somatostatin analogues ( [Ga]Ga-DOTATATE and [Lu]Lu-DOTATATE) have been used to diagnose, monitor, and treat neuroendocrine tumour (NET) patients with...
: Radiolabeled somatostatin analogues ( [Ga]Ga-DOTATATE and [Lu]Lu-DOTATATE) have been used to diagnose, monitor, and treat neuroendocrine tumour (NET) patients with great success. [F]AlF-NOTA-octreotide, a promising F-labeled somatostatin analogue and potential alternative for Ga-DOTA-peptides, is under clinical evaluation. However, ideally, the same precursor (combination of chelator-linker-vector) can be used for production of both diagnostic and therapeutic radiopharmaceuticals with very similar ( AlF-method in combination with therapeutic radiometals Bi/Lu) or identical ( complementary Tb-radionuclides) pharmacokinetic properties, allowing for accurate personalised dosimetry estimation and radionuclide therapy of NET patients. In this study we evaluated 3p--NETA, as potential theranostic AlF-chelator and present first results of radiosynthesis and preclinical evaluation of [F]AlF-3p--NETA-TATE. : 3p--NETA was synthesized and radiolabeled with diagnostic (Ga, AlF) or therapeutic (Lu, Tb, Bi, Ac and Cu) radionuclides at different temperatures (25-95 °C). The stability of the corresponding radiocomplexes was determined in phosphate-buffered saline (PBS) and human serum. 3p--NETA-TATE was synthesized using standard solid/liquid-phase peptide synthesis. [F]AlF-3p--NETA-TATE was synthesized in an automated AllinOne® synthesis module and the stability of [F]AlF-3p--NETA-TATE was evaluated in formulation buffer, PBS and human serum. [F]AlF-3p--NETA-TATE pharmacokinetics were evaluated using µPET/MRI in healthy rats, with [F]AlF-NOTA-Octreotide as benchmark. : 3p--NETA quantitatively sequestered Lu, Bi and Cu at 25 °C while heating was required to bind AlF, Ga, Tb and Ac efficiently. The [F]AlF-, [Lu]Lu- and [Tb]Tb-3p--NETA-complex showed excellent stability in both PBS and human serum over the study period. In contrast, [Cu]Cu- and [Ac]Ac-, [Ga]Ga-3p--NETA were stable in PBS, but not in human serum. [F]AlF-3p--NETA-TATE was obtained in good radiochemical yield and radiochemical purity. [F]AlF-3p--NETA-TATE displayed good stability for 4 h in all tested conditions. Finally, [F]AlF-3p--NETA-TATE showed excellent pharmacokinetic properties comparable with the results obtained for [F]AlF-NOTA-Octreotide. : 3p--NETA is a versatile chelator that can be used for both diagnostic applications (AlF) and targeted radionuclide therapy (Bi, Lu, Tb). It has the potential to be the new theranostic chelator of choice for clinical applications in nuclear medicine.
Topics: Animals; Chelating Agents; Fluorine Radioisotopes; Gallium Radioisotopes; Humans; Neuroendocrine Tumors; Octreotide; Positron-Emission Tomography; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Rats; Somatostatin
PubMed: 35966589
DOI: 10.7150/thno.75336 -
European Journal of Nuclear Medicine... Jul 2023A series of radiotracers targeting fibroblast activation protein (FAP) with great pharmacokinetics have been developed for cancer diagnosis and therapy. Nevertheless,...
PURPOSE
A series of radiotracers targeting fibroblast activation protein (FAP) with great pharmacokinetics have been developed for cancer diagnosis and therapy. Nevertheless, the use of dominant PET tracers, gallium-68-labeled FAPI derivatives, was limited by the short nuclide half-life and production scale, and the therapeutic tracers exhibited rapid clearance and insufficient tumor retention. In this study, we developed a FAP targeting ligand, LuFL, containing organosilicon-based fluoride acceptor (SiFA) and DOTAGA chelator, capable of labeling fluorine-18 and lutetium-177 in one molecular with simple and highly efficient labeling procedure, to achieve cancer theranostics.
METHODS
The precursor LuFL (20) and [Lu]Lu-LuFL (21) were successfully synthesized and labeled with fluorine-18 and lutetium-177 using a simple procedure. A series of cellular assays were performed to characterize the binding affinity and FAP specificity. PET imaging, SPECT imaging, and biodistribution studies were conducted to evaluate pharmacokinetics in HT-1080-FAP tumor-bearing nude mice. A comparison study of [Lu]Lu-LuFL ([Lu]21) and [Lu]Lu-FAPI-04 was carried out in HT-1080-FAP xenografts to determine the cancer therapeutic efficacy.
RESULTS
LuFL (20) and [Lu]Lu-LuFL (21) demonstrated excellent binding affinity towards FAP (IC: 2.29 ± 1.12 nM and 2.53 ± 1.87 nM), compared to that of FAPI-04 (IC: 6.69 ± 0.88 nM). In vitro cellular studies showed that F-/Lu-labeled 21 displayed high specific uptake and internalization in HT-1080-FAP cells. Micro-PET, SPECT imaging and biodistribution studies with [F]/[Lu]21 revealed higher tumor uptake and longer tumor retention than those of [ Ga]/[Lu]Ga/Lu-FAPI-04. The radionuclide therapy studies showed significantly greater inhibition of tumor growth for the [Lu]21 group, than for the control group and the [Lu]Lu-FAPI-04 group.
CONCLUSION
The novel FAPI-based radiotracer containing SiFA and DOTAGA was developed as a theranostics radiopharmaceutical with simple and short labeling process, and showed promising properties including higher cellular uptake, better FAP binding affinity, higher tumor uptake and prolong retention compared to FAPI-04. Preliminary experiments with F- and Lu-labeled 21 showed promising tumor imaging properties and favorable anti-tumor efficacy.
Topics: Mice; Animals; Humans; Tissue Distribution; Ligands; Precision Medicine; Mice, Nude; Positron-Emission Tomography; Fluorine Radioisotopes; Neoplasms; Gallium Radioisotopes; Fibroblasts; Cell Line, Tumor; Positron Emission Tomography Computed Tomography
PubMed: 36864362
DOI: 10.1007/s00259-023-06169-5 -
International Journal of Pharmaceutics Aug 2022Nuclear medicine imaging plays an important role in nanomedicine. However, it is still challenging to develop a versatile platform to make the nonviral nanovectors used...
Nuclear medicine imaging plays an important role in nanomedicine. However, it is still challenging to develop a versatile platform to make the nonviral nanovectors used in cancer therapy biotraceable. In the present study, a robust approach to radiolabel inorganic nanovectors for SPECT and PET imaging was developed. The approach was based on the bisphosphonates (BP) conjugated on the nanovector, mesoporous silicon (PSi) nanoparticles. BP served as an efficient chelator for various radionuclides. For both of the Tc and Ga radionuclides utilized, the radiochemical purity and radiochemical yield were ∼99% and ∼90%, respectively. Because of the short decay time of the radionuclides, an easy, fast and effective PEGylation method was developed to improve the residence time in systemic circulation. Both PEG-Tc-BP-PSi and PEG-Ga-BP-PSi NPs, where PEGylation was performed after the labeling, had excellent colloidal and radiochemical stability in vitro. The plain particles without PEGylation accumulated fast in the reticuloendothelial system organs upon intravenous administration, while PEGylation prolonged the residence time of the particles in systemic circulation. Overall, the developed approach proved to be applicable for labeling nonviral nanovectors with various radionuclides easily and robustly. Considering the nature of mesoporous nanoparticles, the approach does not hamper the addition of other functionalities on the vector, nor its capability to carry high payloads.
Topics: Gallium Radioisotopes; Nanomedicine; Nanoparticles; Radiopharmaceuticals; Silicon; Tomography, Emission-Computed, Single-Photon
PubMed: 35902052
DOI: 10.1016/j.ijpharm.2022.122040 -
European Journal of Nuclear Medicine... Sep 2023
Topics: Humans; Muscles; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography; Gallium Radioisotopes; Fluorodeoxyglucose F18; Quinolines; Fibroblasts
PubMed: 37272954
DOI: 10.1007/s00259-023-06263-8 -
Journal of Nuclear Medicine : Official... Sep 2021Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. A growing number of local and systemic...
Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. A growing number of local and systemic therapies are available, and accurate staging is critical for management decisions. We assessed the impact of neovasculature imaging by Ga-PSMA-11 PET/CT on disease staging, prognostic groups, and management of patients with HCC compared with staging with CT. Forty patients who received imaging with Ga-PSMA-11 PET/CT for HCC staging between September 2018 and September 2019 were retrospectively included. Management before and after PET scanning was assessed by standardized surveys. The presence of HCC was evaluated by 3 masked readers on a per-patient and per-region basis for PET/CT (PET criteria) and multiphase contrast-enhanced CT (CT criteria) in separate sessions. Lesions were validated by follow-up imaging or histopathology, and progression-free survival was recorded. Endpoints were detection rate and positive predictive value for Ga-PSMA-11 PET versus CT, interreader reproducibility, and changes in stage, prognostic groups, and management plans. Median age was 65 y (range, 37-81 y), and median Child-Pugh score was 5 (range, 5-9). Most patients were treatment-naïve (27/40, 67.5%). The sensitivity of PET versus CT to identify liver lesions for patients with lesion validation was 31 of 32 (97%) for both modalities, whereas it was 6 of 6 (100%) versus 4 of 6 (67%), respectively, for extrahepatic lesions. PET and CT each had a positive predictive value of 100% at the liver level. PET versus CT stage was congruent in 30 of 40 (75%) patients; upstaging was seen in 8 of 40 patients (20%), whereas 2 of 40 (5%) had downstaging by PET. Intended management changed in 19 of 40 patients (47.5%); 9 of 19 of these patients were found to have detectable distant metastases (47.4%) and assigned stage 4 disease, most of whom were shifted to systemic therapy (8/9, 89%). Two patients underwent Lu-PSMA-617 radioligand therapy. Median progression-free survival was 5.2 mo for the entire cohort; 5.3 mo for PET M0, and 4.7 mo for PET M1 patients, respectively. Ga-PSMA-11 PET demonstrated higher accuracy than CT in the detection of HCC metastases and was associated with a management change in about half the patient cohort.
Topics: Aged; Carcinoma, Hepatocellular; Gallium Isotopes; Gallium Radioisotopes; Humans; Liver Neoplasms; Middle Aged; Positron Emission Tomography Computed Tomography
PubMed: 33509970
DOI: 10.2967/jnumed.120.257915 -
Molecules (Basel, Switzerland) Oct 2023KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly...
KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly understood. We aimed to gain insight into these issues using gallium-67 and gallium-68 as radiotracers with SPECT and PET imaging in mice. [Ga]KP46 and [Ga]KP46, compared with [Ga]gallium acetate, were used for log measurements, in vitro cell uptake studies in A375 melanoma cells, and in vivo imaging in mice bearing A375 tumour xenografts up to 48 h after intravenous (tracer level) and oral (tracer and bulk) administration. Ga was more efficiently accumulated in A375 cells in vitro when presented as [Ga]KP46 than as [Ga]gallium acetate, but the reverse was observed when intravenously administered in vivo. After oral administration of [Ga]KP46, absorption of Ga and Ga from the GI tract and delivery to tumours were poor, with the majority excreted in faeces. By 48 h, low but measurable amounts were accumulated in tumours. The distribution in tissues of absorbed radiogallium and octanol extraction of tissues suggested trafficking as free gallium rather than as KP46. We conclude that KP46 likely acts as a slow releaser of gallium ions which are inefficiently absorbed from the GI tract and trafficked to tissues, including tumour and bone.
Topics: Humans; Animals; Mice; Gallium Radioisotopes; Gallium; Organometallic Compounds; Antineoplastic Agents; Neoplasms; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Acetates
PubMed: 37894695
DOI: 10.3390/molecules28207217