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International Journal of Molecular... Jan 2022The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also... (Meta-Analysis)
Meta-Analysis Review
The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide.
Topics: Biomarkers; Clinical Decision-Making; Disease Management; Drug Monitoring; Humans; Molecular Targeted Therapy; Obesity; Organ Specificity; Prognosis; Radiopharmaceuticals; Treatment Outcome
PubMed: 35055005
DOI: 10.3390/ijms23020818 -
European Journal of Nuclear Medicine... Apr 2017The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer Ga-PSMA-11 shows great promise in the detection of prostate cancer....
PURPOSE
The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of F-labelled analogs. F-PSMA-1007 was selected among several F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of F-PSMA-1007 in human volunteers and patients.
METHODS
Radiation dosimetry of F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining.
RESULTS
With an effective dose of approximately 4.4-5.5 mSv per 200-250 MBq examination, F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2-3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter.
CONCLUSION
F-PSMA-1007 performs at least comparably to Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of Ga-labelled PSMA-targeted tracers.
Topics: Aged; Antigens, Surface; Fluorine Radioisotopes; Glutamate Carboxypeptidase II; Humans; Lymphatic Metastasis; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiation Dosage; Radiopharmaceuticals; Renal Elimination; Tissue Distribution
PubMed: 27889802
DOI: 10.1007/s00259-016-3573-4 -
Theranostics 2023Radiopharmaceutical therapy (RPT) has proven to be an effective cancer treatment with minimal toxicity. With several RPT agents approved by FDA, the remarkable potential... (Review)
Review
Radiopharmaceutical therapy (RPT) has proven to be an effective cancer treatment with minimal toxicity. With several RPT agents approved by FDA, the remarkable potential of this therapy is now being recognized, and the anti-tumor immunity induced by RPT is beginning to be noticed. This review evaluates the potential of RPT for immune activation, including promoting the release of danger associated-molecular pattern molecules that recruit inflammatory cells into the tumor microenvironment, and activating antigen-presenting cells and cytotoxic T cells. We also discuss the progress of combining RPT with immunotherapy to increase efficacy.
Topics: Humans; Radiopharmaceuticals; Hot Temperature; Neoplasms; T-Lymphocytes, Cytotoxic; Immunotherapy; Tumor Microenvironment
PubMed: 36632233
DOI: 10.7150/thno.79806 -
Molecular Imaging and Biology Feb 2022In oncology, biomarker research aimed to provide insights on cancer biology via positron emission tomography (PET) and single photon emission tomography (SPECT) imaging... (Review)
Review
In oncology, biomarker research aimed to provide insights on cancer biology via positron emission tomography (PET) and single photon emission tomography (SPECT) imaging has seen an incredible growth in the past two decades. Despite the increased number of publications on PET/SPECT radiopharmaceuticals, the field lacked standardization of in vitro and in vivo parameters necessary for the characterization of any radiotracer. Through the efforts of the World Molecular Imaging Society Education Committee, this white paper lays down validation studies that are essential to chemically and biologically characterize new radiopharmaceuticals derived from small molecules, peptides or proteins. Finally, a brief overview of the steps toward translation is also presented.Herein, we discuss the following: Chemistry and radiochemistry metrics to establish the identity of the imaging agent. In vitro and in vivo studies to examine the radiotracer's mechanism of action, which includes target specificity, pharmacokinetics and in vivo metabolism.
Topics: Medical Oncology; Positron-Emission Tomography; Radiochemistry; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon
PubMed: 34542804
DOI: 10.1007/s11307-021-01645-6 -
European Journal of Nuclear Medicine... Jul 2017Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions,... (Review)
Review
PURPOSE
Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions, and effectiveness of these. The aims of this study are to estimate the incidence of extravasation of diagnostic and therapeutic radiopharmaceuticals, to evaluate medical consequences, and to evaluate medical treatment applied subsequently to those incidents.
METHODS
A sensitive and elaborate literature search was performed in Embase and PubMed using the keywords "misadministration", "extravasation", "paravascular infiltration", combined with "tracer", "radionuclide", "radiopharmaceutical", and a list of keywords referring to clinically used tracers (i.e. "Technetium-99m", "Yttrium-90"). Reported data on radiopharmaceutical extravasation and applied interventions was extracted and summarised.
RESULTS
Thirty-seven publications reported 3016 cases of diagnostic radiopharmaceutical extravasation, of which three cases reported symptoms after extravasation. Eight publications reported 10 cases of therapeutic tracer extravasation. The most severe symptom was ulceration. Thirty-four different intervention and prevention strategies were performed or proposed in literature.
CONCLUSIONS
Extravasation of diagnostic radiopharmaceuticals is common. Tc, I, F, and Ga labelled tracers do not require specific intervention. Extravasation of therapeutic radiopharmaceuticals can give severe soft tissue lesions. Although not evidence based, surgical intervention should be considered. Furthermore, dispersive intervention, dosimetry and follow up is advised. Pharmaceutical intervention has no place yet in the immediate care of radiopharmaceutical extravasation.
Topics: Humans; Radiopharmaceuticals
PubMed: 28303300
DOI: 10.1007/s00259-017-3675-7 -
International Journal of Radiation... Mar 2021In radiopharmaceutical therapy (RPT), a radionuclide is systemically or locally delivered with the goal of targeting and delivering radiation to cancer cells while... (Review)
Review
In radiopharmaceutical therapy (RPT), a radionuclide is systemically or locally delivered with the goal of targeting and delivering radiation to cancer cells while minimizing radiation exposure to untargeted cells. Examples of current RPTs include thyroid ablation with the administration of I, treatment of liver cancer with Y microspheres, the treatment of bony metastases with Ra, and the treatment of neuroendocrine tumors with Lu-DOTATATE. New RPTs are being developed where radionuclides are incorporated into systemic targeted therapies. To assure that RPT is appropriately implemented, advances in targeting need to be matched with advances in quantitative imaging and dosimetry methods. Currently, radiopharmaceutical therapy is administered by intravenous or locoregional injection, and the treatment planning has typically been implemented like chemotherapy, where the activity administered is either fixed or based on a patient's body weight or body surface area. RPT pharmacokinetics are measurable by quantitative imaging and are known to vary across patients, both in tumors and normal tissues. Therefore, fixed or weight-based activity prescriptions are not currently optimized to deliver a cytotoxic dose to targets while remaining within the tolerance dose of organs at risk. Methods that provide dose estimates to individual patients rather than to reference geometries are needed to assess and adjust the injected RPT dose. Accurate doses to targets and organs at risk will benefit the individual patients and decrease uncertainties in clinical trials. Imaging can be used to measure activity distribution in vivo, and this information can be used to determine patient-specific treatment plans where the dose to the targets and organs at risk can be calculated. The development and adoption of imaging-based dosimetry methods is particularly beneficial in early clinical trials. In this work we discuss dosimetric accuracy needs in modern radiation oncology, uncertainties in the dosimetry in RPT, and best approaches for imaging and dosimetry of internal radionuclide therapy.
Topics: Calibration; Clinical Trials as Topic; Humans; Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Image-Guided; Single Photon Emission Computed Tomography Computed Tomography
PubMed: 32805300
DOI: 10.1016/j.ijrobp.2020.08.035 -
Journal of Nuclear Medicine : Official... Oct 2022The application of radiopharmaceutical therapy for the treatment of certain diseases is well established, and the field is expanding. New therapeutic...
The application of radiopharmaceutical therapy for the treatment of certain diseases is well established, and the field is expanding. New therapeutic radiopharmaceuticals have been developed in recent years, and more are in the research pipeline. Concurrently, there is growing interest in the use of internal dosimetry as a means of personalizing, and potentially optimizing, such therapy for patients. Internal dosimetry is multifaceted, and the current state of the art is discussed in this continuing education article. Topics include the context of dosimetry, internal dosimetry methods, the advantages and disadvantages of incorporating dosimetry calculations in radiopharmaceutical therapy, a description of the workflow for implementing patient-specific dosimetry, and future prospects in the field.
Topics: Humans; Radiometry; Radiopharmaceuticals
PubMed: 36192334
DOI: 10.2967/jnumed.121.262305 -
Revista de Salud Publica (Bogota,... 2008There has been considerable under-reporting of drug and radiopharmaceutical interactions, security and adverse reactions. The increasing use of radiopharmaceuticals has... (Review)
Review
There has been considerable under-reporting of drug and radiopharmaceutical interactions, security and adverse reactions. The increasing use of radiopharmaceuticals has come to the attention of nuclear medicine staff and regulatory bodies. The aim is to provide reference for adverse reactions which could help all nuclear medicine staff in their daily routine. Reporting adverse events, including situations where an adverse event may have occurred but was actually avoided, is essential when assessing the magnitude of problems, alerting health professionals to these problems and ultimately for improving diagnostic accuracy.
Topics: Drug Interactions; Humans; Radiopharmaceuticals
PubMed: 19043639
DOI: 10.1590/s0124-00642008000300013 -
Journal of Nuclear Medicine : Official... Dec 2014Theranostic nanoparticles hold the potential to revolutionize disease management. Over the last decade, there has been growing interest in the engineering of various... (Review)
Review
Theranostic nanoparticles hold the potential to revolutionize disease management. Over the last decade, there has been growing interest in the engineering of various kinds of theranostic nanoparticles for simultaneous cancer imaging and therapy in small animals. Efficient targeting of theranostic nanoparticles to the tumor site is critical for both diagnosis and therapy. However, difficulties still exist in the engineering of biocompatible theranostic nanoparticles with highly specific in vivo tumor-targeting capabilities. Here, we discuss the current and prospective status of theranostic nanoparticles that actively target tumors, as well as the challenges that still exist.
Topics: Humans; Nanoparticles; Neoplasms; Radionuclide Imaging; Radiopharmaceuticals
PubMed: 25413134
DOI: 10.2967/jnumed.114.146019 -
Journal of Nuclear Medicine : Official... Dec 2022Radiopharmaceutical therapy is an emerging treatment modality that has demonstrated increasing importance as a significant component in the treatment of cancer. Prostate... (Review)
Review
Radiopharmaceutical therapy is an emerging treatment modality that has demonstrated increasing importance as a significant component in the treatment of cancer. Prostate cancer (PCa) remains one of the commonest solid-organ tumors and is associated with significant societal burdens. Despite significant disease heterogeneity, PCa remains an ideal candidate for radiopharmaceutical therapy because of the prolonged disease course, metastatic disease tropism, and sensitivity to radiation therapy. To date, advanced PCa remains one of the most successful arenas for the development and approval of radiopharmaceutical agents. In this review, we aim to summarize the complex processes required to obtain regulatory approval for a novel agent and highlight the limitations and hurdles specific to the approval of radiopharmaceutical agents. In advanced PCa, we outline the importance of a framework for trial design with respect to defining disease state and acceptable outcome measures-as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG). Finally, using the principles mandated by the Food and Drug Administration approval process and the framework provided by the PCWG, we outline experience with the successful approval of the radiopharmaceutical agents Ra and Lu-PSMA-617.
Topics: United States; Male; Humans; Precision Medicine; Drug Approval; Radiopharmaceuticals; United States Food and Drug Administration; Prostatic Neoplasms
PubMed: 36456108
DOI: 10.2967/jnumed.121.263301