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Journal of Nuclear Medicine : Official... May 2021Treatment of advanced metastatic castration-resistant prostate cancer after failure of approved therapy options remains challenging. Prostate-specific membrane antigen...
Treatment of advanced metastatic castration-resistant prostate cancer after failure of approved therapy options remains challenging. Prostate-specific membrane antigen (PSMA)-targeting β- and α-emitters have been introduced, with promising response rates. Here, we present the first-to our knowledge-clinical data for PSMA-targeted α-therapy (TAT) using Ac-PSMA imaging and therapy (I&T). Fourteen patients receiving Ac-PSMA-I&T were included in this retrospective analysis. Eleven of the 14 had prior second-line antiandrogen treatment with abiraterone or enzalutamide, prior chemotherapy, and prior Lu-PSMA treatment. Patients were treated at bimonthly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) was measured for response assessment. Hematologic and nonhematologic side effects were recorded according to the Common Terminology Criteria for Adverse Events, version 5.0. Thirty-four cycles of Ac-PSMA-I&T were applied (median dose, 7.8 MBq; range, 6.0-8.5), with 1 cycle in 3 patients, 2 cycles in 7 patients, 4 cycles in 3 patients, and 5 cycles in 1 patient. No acute toxicity was observed during hospitalization. Baseline PSA was 112 ng/mL (range, 20.5-818 ng/mL). The best PSA response after TAT (a PSA decline ≥ 50%) was observed in 7 patients, and a PSA decline of any amount was observed in 11 patients. Three patients had no PSA decline at any time. A subgroup analysis of 11 patients with prior Lu-PSMA treatment showed any PSA decline in 8 patients and a decline of at least 50% in 5 patients. After TAT, grade 3 anemia was observed in 3 of the 14 patients, with 2 of them presenting with grade 2 anemia already at baseline. Grade 3 leukopenia was observed in 1 patient. Eight patients with preexisting xerostomia after Lu-PSMA showed no worsening after TAT. Newly diagnosed grade 1 or 2 xerostomia after TAT was observed in 5 patients. One patient reported no xerostomia at all. Our first clinical data for TAT using Ac-PSMA-I&T showed a promising antitumor effect in advanced metastatic castration-resistant prostate cancer. These results are highly comparable to data on Ac-PSMA-617 TAT.
Topics: Actinium; Antigens, Surface; Beta Particles; Glutamate Carboxypeptidase II; Humans; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Treatment Outcome
PubMed: 33008928
DOI: 10.2967/jnumed.120.251017 -
Journal of Nuclear Medicine : Official... Dec 2016Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled...
UNLABELLED
Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to Ac-PSMA-617 therapy.
METHODS
Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with Ga-PSMA-11 PET/CT.
RESULTS
Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect.
CONCLUSION
Targeted α-therapy with Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients.
Topics: Actinium; Alpha Particles; Antigens, Surface; Beta Particles; Dipeptides; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes
PubMed: 27390158
DOI: 10.2967/jnumed.116.178673 -
Seminars in Radiation Oncology Jan 2021In the current era of precision medicine, there is renewed interest in radiopharmaceutical therapy and theranostics. The approval of somatostatin receceptor directed... (Review)
Review
In the current era of precision medicine, there is renewed interest in radiopharmaceutical therapy and theranostics. The approval of somatostatin receceptor directed therapy and norepinephrine transporter targeted I-MIBG therapies by the FDA and the rapid progress of highly promising beta and alpha emitter tagged PSMA directed therapy of prostate cancer have stimulated clinically impactful changes in practice. Many novel strategies are being explored and novel radiopharmaceutical therapeutic agents including peptide based ligands as well as antibodies or antibody fragments are being developed preclinically or are in early phase clinical trials. While beta particle emitters have most commonly been used for targeted radiotherapy and radioimmunotargeting, there is an emerging interest in alpha emitters that cause greater density of ionization events leading to increased double-strand DNA damage and cluster breaks because of the high-energy particles within a shorter tissue range of penetration and thereby lower toxicity to adjacent normal tissues.
Topics: Humans; Male; Precision Medicine; Prostatic Neoplasms; Radiopharmaceuticals
PubMed: 33246639
DOI: 10.1016/j.semradonc.2020.07.010 -
Medical Physics Jun 2017Conventional charged-particle imaging techniques - such as autoradiography - provide only two-dimensional (2D) black ex vivo images of thin tissue slices. In order to...
PURPOSE
Conventional charged-particle imaging techniques - such as autoradiography - provide only two-dimensional (2D) black ex vivo images of thin tissue slices. In order to get volumetric information, images of multiple thin slices are stacked. This process is time consuming and prone to distortions, as registration of 2D images is required. We propose a direct three-dimensional (3D) autoradiography technique, which we call charged-particle emission tomography (CPET). This 3D imaging technique enables imaging of thick tissue sections, thus increasing laboratory throughput and eliminating distortions due to registration. CPET also has the potential to enable in vivo charged-particle imaging with a window chamber or an endoscope.
METHODS
Our approach to charged-particle emission tomography uses particle-processing detectors (PPDs) to estimate attributes of each detected particle. The attributes we estimate include location, direction of propagation, and/or the energy deposited in the detector. Estimated attributes are then fed into a reconstruction algorithm to reconstruct the 3D distribution of charged-particle-emitting radionuclides. Several setups to realize PPDs are designed. Reconstruction algorithms for CPET are developed.
RESULTS
Reconstruction results from simulated data showed that a PPD enables CPET if the PPD measures more attributes than just the position from each detected particle. Experiments showed that a two-foil charged-particle detector is able to measure the position and direction of incident alpha particles.
CONCLUSIONS
We proposed a new volumetric imaging technique for charged-particle-emitting radionuclides, which we have called charged-particle emission tomography (CPET). We also proposed a new class of charged-particle detectors, which we have called particle-processing detectors (PPDs). When a PPD is used to measure the direction and/or energy attributes along with the position attributes, CPET is feasible.
Topics: Algorithms; Imaging, Three-Dimensional; Tomography, Emission-Computed
PubMed: 28370094
DOI: 10.1002/mp.12245 -
IARC Monographs on the Evaluation of... 2012
Review
Topics: Alpha Particles; Beta Particles; Gamma Rays; Humans; Neoplasms, Radiation-Induced; Skin Neoplasms; Sunlight; Ultraviolet Rays; X-Rays
PubMed: 23189752
DOI: No ID Found -
International Journal of Molecular... May 2019In the last two decades, various nanomaterials have attracted increasing attention in medical science owing to their unique physical and chemical characteristics.... (Review)
Review
In the last two decades, various nanomaterials have attracted increasing attention in medical science owing to their unique physical and chemical characteristics. Incorporating radionuclides into conventionally used nanomaterials can confer useful additional properties compared to the original material. Therefore, various radionuclides have been used to synthesize functional nanomaterials for biomedical applications. In particular, several α- or β-emitter-labeled organic and inorganic nanoparticles have been extensively investigated for efficient and targeted cancer treatment. This article reviews recent progress in cancer therapy using radiolabeled nanomaterials including inorganic, polymeric, and carbon-based materials and liposomes. We first provide an overview of radiolabeling methods for preparing anticancer agents that have been investigated recently in preclinical studies. Next, we discuss the therapeutic applications and effectiveness of α- or β-emitter-incorporated nanomaterials in animal models and the emerging possibilities of these nanomaterials in cancer therapy.
Topics: Animals; Humans; Nanostructures; Radioisotopes
PubMed: 31083402
DOI: 10.3390/ijms20092323 -
Seminars in Nuclear Medicine Mar 2020Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms, arising from cells of the endocrine system, with various clinical behaviors. Although these neoplasms... (Review)
Review
Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms, arising from cells of the endocrine system, with various clinical behaviors. Although these neoplasms are considered rare, a significant increase in the incidence and detectability of NET has been noted in many epidemiological studies in recent years. Among the various therapeutic options, peptide receptor radionuclide therapy (PRRT), using somatostatine has been shown to be highly effective and a well-tolerated therapy, improving survival parameters. The current use of radionuclides for PRRT is β-emitters. Due to hypoxia cancer tissue could be resistant for β-emitters. Quite long penetration range had a significant impact on side effects. α-particles with higher energy and shorter penetration range in comparison to β-particles, have distinct advantages for use in targeted therapy. The clinical experience with somatostatine based targeted α therapy (TAT) in NET showed very promising results even in patienicts refractory to treatment with β-emitters. This article summarizes current developments in preclinical and clinical investigation on TAT in NET.
Topics: Alpha Particles; Animals; Clinical Trials as Topic; Humans; Molecular Targeted Therapy; Neuroendocrine Tumors; Treatment Outcome
PubMed: 32172802
DOI: 10.1053/j.semnuclmed.2019.11.003 -
The Journal of Clinical Endocrinology... Apr 2022Thyroid function status has effects on the development of atherosclerotic cardiovascular disease by affecting lipid metabolism, but associations of high-density...
CONTEXT
Thyroid function status has effects on the development of atherosclerotic cardiovascular disease by affecting lipid metabolism, but associations of high-density lipoprotein (HDL) particle concentrations and subfractions with thyroid hormone levels within the reference range remain elusive.
OBJECTIVE
The aim of the present study was to determine the associations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels with HDL particle characteristics in euthyroid individuals.
METHODS
This cross-sectional study on the associations of thyroid hormones with HDL particle concentrations, HDL subfractions, and HDL particle size included 5844 euthyroid individuals (FT3, FT4, and TSH levels within the reference range and no medication use affecting thyroid function), participating in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. HDL particles and subfractions were measured by nuclear magnetic resonance using an optimized version of the NMR LipoProfile Test (LP4).
RESULTS
In multivariable linear regression analyses, FT3 was positively associated with total HDL particle concentration (std.β = 0.14; P < 0.001) and with small (std.β = 0.13; P < 0.001) and medium-sized HDL particles (std.β = 0.05; P = 0.001). Conversely, FT3 was inversely associated with large HDL particles (std.β = -0.07; P < 0.001) and with HDL particle size (std.β = -0.08; P < 0.001). Such associations with FT4 or reciprocally with TSH were less pronounced or nonsignificant.
CONCLUSION
In euthyroid individuals, higher FT3 is cross-sectionally associated with higher total HDL particle concentration and with lower HDL particle size. These associations may be relevant to better understand the role of HDL in thyroid function-associated atherosclerotic cardiovascular disease.
Topics: Humans; Cross-Sectional Studies; Particle Size; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine; Thyroid Gland; Atherosclerosis
PubMed: 35106588
DOI: 10.1210/clinem/dgac044