Comparison of Calculated Radiation Delivery Versus Actual Radiation Delivery in Military Macaws (Ara militaris)

The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3–7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.

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Translational Research in FLASH Radiotherapy—From Radiobiological Mechanisms to In Vivo Results

Biomedicines ◽

10.3390/biomedicines9020181 ◽

2021 ◽

Vol 9 (2) ◽

pp. 181

Author(s):

Loredana G. Marcu ◽

Eva Bezak ◽

Dylan D. Peukert ◽

Puthenparampil Wilson

Keyword(s):

Dose Rate ◽

High Dose Rate ◽

Current Status ◽

Therapeutic Window ◽

High Dose ◽

Linear Accelerators ◽

Radiation Delivery ◽

Tissue Sparing

FLASH radiotherapy, or the administration of ultra-high dose rate radiotherapy, is a new radiation delivery method that aims to widen the therapeutic window in radiotherapy. Thus far, most in vitro and in vivo results show a real potential of FLASH to offer superior normal tissue sparing compared to conventionally delivered radiation. While there are several postulations behind the differential behaviour among normal and cancer cells under FLASH, the full spectra of radiobiological mechanisms are yet to be clarified. Currently the number of devices delivering FLASH dose rate is few and is mainly limited to experimental and modified linear accelerators. Nevertheless, FLASH research is increasing with new developments in all the main areas: radiobiology, technology and clinical research. This paper presents the current status of FLASH radiotherapy with the aforementioned aspects in mind, but also to highlight the existing challenges and future prospects to overcome them.

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A Call to Define Stereotactic Radiosurgery

Neurosurgery ◽

10.1227/01.neu.0000143613.13759.d4 ◽

2004 ◽

Vol 55 (6) ◽

pp. 1371-1373 ◽

Cited By ~ 18

Author(s):

Bruce E. Pollock ◽

L Dade Lunsford

Keyword(s):

Radiation Therapy ◽

Stereotactic Radiosurgery ◽

Single Session ◽

Short History ◽

Effective Radiation Dose ◽

The Past ◽

Radiation Delivery ◽

History Of ◽

Effective Radiation ◽

And Training

Abstract STEREOTACTIC RADIOSURGERY IS the single-session, precise delivery of a therapeutically effective radiation dose to an imaging-defined target. Conceived and developed during the past 5 decades, stereotactic radiosurgery has involved significant advances, which have improved patient outcomes and made it a critical component of modern neurosurgical practice and training. In this article, a short history of stereotactic surgery and radiosurgery are presented, and radiosurgery is contrasted to radiation therapy. Adherence to accepted, descriptive terms in defining stereotactic radiosurgery and radiation therapy permits a clear distinction among the results of the different radiation delivery techniques for patients, physicians, and other interested parties.

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The Downside of Radiosurgery, Possible Complications

JBNC - JORNAL BRASILEIRO DE NEUROCIRURGIA ◽

10.22290/jbnc.v25i3.1141 ◽

2018 ◽

Vol 25 (3) ◽

pp. 286-299

Author(s):

Luiz Claudio Modesto Pereira ◽

Valeria Patricia De Araujo ◽

Thiago Henrique de Moraes Modesto

Keyword(s):

Tumor Imaging ◽

Neurological Complications ◽

Normal Brain ◽

Radiation Delivery ◽

Cranial Nerve Dysfunction ◽

Technological Advances ◽

Treatment Dose ◽

Barrier Breakdown ◽

Nerve Dysfunction ◽

Blood Brain Barrier Breakdown

As a consequence of various last century scientific and technological advances radiotherapy and stereotactic radiosurgery (SRS) have emerged as safe and efficacious techniques for the treatment of various intracranial pathologies. Recent improvements such as in brain and tumor imaging, patient immobilization, 3D planning and radiation delivery allow it to target lesions more accurately and minimize radiation delivered to normal brain, leading to drastic improvements in terms of safety and post-therapy complication. Despite that SRS still implies in moderate to severe side effects in one fifth to one fourth of patients. Fortunately the most common SRS complications, such as edema, blood brain barrier breakdown and MRI abnormalities are self-limited and amenable to treatment. The precise pathophysiological processes of SRS complications are still under research, however multiple factors including treatment dose, modality and planning complexity, target size, shape and location are known to affect treatment results. The most reported potential SRS complications are ischemic stroke, brain or lesion hemorrhage, radiosurgeryinduced neoplasm, radiation necrosis, white matter changes, cranial nerve dysfunction and cognition problems. SRS induced neurological complications may persist only in as much as 5% of patients.

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Application of Current Radiation Delivery Systems and Radiobiology

Principles of Neurological Surgery ◽

10.1016/b978-1-4377-0701-4.00045-2 ◽

2012 ◽

pp. 697-706

Author(s):

Jay Loeffler ◽

Helen Shih ◽

Melin Khandekar

Keyword(s):

Delivery Systems ◽

Radiation Delivery

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Predictability of Elimination and Excretion of Small Molecules from Animals to Humans, and Impact on Dosimetry for human ADME Studies with Radiolabeled Drugs

Current Clinical Pharmacology ◽

10.2174/1574884716666210309103625 ◽

2021 ◽

Vol 16 ◽

Author(s):

Ad Roffel ◽

Jan Jaap van Lier ◽

Gerk Rozema ◽

Ewoud-Jan van Hoogdalem

Keyword(s):

Small Molecules ◽

Half Life ◽

Fecal Excretion ◽

Radiation Burden ◽

Quantitative Correlation ◽

Elimination Half ◽

The Impact ◽

Plasma Half Life ◽

Entire Dataset ◽

Actual Radiation

Background: We assessed the extent to which urinary and fecal excretion of 14C-labeled drug material in animal ADME studies was predictive of human ADME studies. We compared observed plasma elimination half lives for total drug related radioactivity in humans to pre-study predictions, and we estimated the impact of any major differences on human dosimetry calculations. Methods: We included 34 human ADME studies with doses of 14C above 0.1 MBq. We calculated ratios of dosimetry input parameters (percentage fecal excretion in humans versus animals; observed half life in humans versus predicted pre-study) and output parameters (effective dose post-study versus pre study) and assessed their relationship. Results: A quantitative correlation assessment did not show a statistically significant correlation between the ratios of percentages of 14C excreted in feces and the ratios of dosimetry outcomes in the entire dataset, but a statistically significant correlation was found when assessing the studies that were based on ICRP 60/62 (n=19 studies; P=0.0028). There also appeared to be a correlation between the plasma half-life ratios and the ratios of dosimetry results. A quantitative correlation assessment showed that there was a statistically significant correlation between these ratios (P<0.0001). Conclusion: In all cases where the plasma elimination half-life for 14C in humans was found to be longer than the predicted value, the radiation burden was still within ICRP Category IIa. Containment of the actual radiation burden below the limit of 1.00 mSv appeared to be determined partly also by our choice to limit 14C doses to 3.7 MBq.

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