Radium-223 dichloride in prostate cancer: proof of principle for the use of targeted alpha treatment in clinical practice

Dizdarevic, Sabina; McCready, Ralph; Vinjamuri, Sobhan

doi:10.1007/s00259-019-04475-5

Cited by 14 publications

(6 citation statements)

References 46 publications

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“…Finally, 227 Th is also the subject of several early-phase clinical trials using antibody targeted vehicles, such as an alternative PSMA construct in mCRPC patients (NCT03724747) 32 , 33 . 227 Th has one principal gamma emission at 236 keV 12 , and is the parent of 223 Ra; thus, its gamma emissions can also be used for imaging.…”

Section: Introductionmentioning

confidence: 99%

Practical considerations for quantitative clinical SPECT/CT imaging of alpha particle emitting radioisotopes

et al. 2021

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Rationale: Alpha particle emitting radiopharmaceuticals are generating considerable interest for the treatment of disseminated metastatic disease. Molecular imaging of the distribution of these agents is critical to safely and effectively maximize the clinical potential of this emerging drug class. The present studies aim to investigate the feasibility and limitations of quantitative SPECT for 223 Ra, 225 Ac and 227 Th. Methods: Three state-of-the-art SPECT/CT systems were investigated: the GE Discovery NM/CT 670, the GE Optima NM/CT 640, and the Siemens Symbia T6. A series of phantoms, including the NEMA IEC Body phantom, were used to compare and calibrate each camera. Additionally, anthropomorphic physical tumor and vertebrae phantoms were developed and imaged to evaluate the quantitative imaging protocol. Results: This work describes and validates a methodology to calibrate each clinical system. The efficiency of each gamma camera was analyzed and compared. Using the calibration factors obtained with the NEMA phantom, we were able to quantify the activity in 3D-printed tissue phantoms with an error of 2.1%, 3.5% and 11.8% for 223 Ra, 225 Ac, and 227 Th, respectively. Conclusion: The present study validates that quantitative SPECT/CT imaging of 223 Ra, 225 Ac, and 227 Th is achievable but that careful considerations for camera configuration are required. These results will aid in future implementation of SPECT-based patient studies and will help to identify the limiting factors for accurate image-based quantification with alpha particle emitting radionuclides.

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Section: Introductionmentioning

confidence: 99%

Practical considerations for quantitative clinical SPECT/CT imaging of alpha particle emitting radioisotopes

et al. 2021

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“…The approved regimen used worldwide consists of a course of six 223 Ra injections with a standard activity of 55 kBq/kg every 4-week [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

The role of dosimetry and biological effects in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study

Sciuto

Rea

Ungania

et al. 2021

J Exp Clin Cancer Res

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Background 223Ra is currently used for treatment of metastatic castration resistant prostate cancer patients (mCRPC) bone metastases with fixed standard activity. Individualized treatments, based on adsorbed dose (AD) in target and non-target tissue, are absolutely needed to optimize efficacy while reducing toxicity of α-emitter targeted therapy. This is a pilot first in human clinical trial aimed to correlate dosimetry, clinical response and biological side effects to personalize 223Ra treatment. Methods Out of 20 mCRPC patients who underwent standard 223Ra treatment and dosimetry, in a subset of 5 patients the AD to target and non-target tissues was correlated with clinical effects and radiation-induced chromosome damages. Before each 223Ra administrations, haematological parameters, PSA and ALP values were evaluated. Additional blood samples were obtained baseline (T0), at 7 days (T7), 30 days (T30) and 180 days (T180) to evaluate chromosome damage. After administration WB planar 223Ra images were obtained at 2–4 and 18–24 h. Treatment response and toxicity were monitored with clinical evaluation, bone scan, 18F-choline-PET/CT, PSA value and ALP while haematological parameters were evaluated weekly after 223Ra injection and 2 months after last cycle. Results 1. a correlation between AD to target and clinical response was evidenced with threshold of 20 Gy as a cut-off to obtain tumor control; 2. the AD to red marrow was lower than 2 Gy in all the patients with no apparently correlation between dosimetry and clinical toxicity. 3. a high dose dependent increase of the number of dicentrics and micronuclei during the course of 223Ra therapy was observed and a linear correlation has been found between blood AD (BAD) and number of dicentrics. Conclusions This study provides some interesting preliminary evidence to be further investigated: dosimetry may be useful to identify a more appropriate 223Ra administered activity predicting AD to target tissue; a dose dependent complex chromosome damage occurs during 223Ra administration and this injury is more evident in heavily pre-treated patients; dosimetry could be used for radioprotection purpose. Trial registration The pilot study has been approved from the Ethics Committee of Regina Elena National Cancer Institute (N:RS1083/18–2111).

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“…Even if advanced prostate cancer is the main pathology targeted with 223 Ra, this radionuclide is under investigation in others pathologies associated with bone metastases such as breast or renal cancer [ 257 , 258 ]. The work on clinical applications with 223 Ra is considerable and detailed reviews can provide more information about the global state of art on 223 Ra but also on the ongoing clinical trials [ 259 , 260 , 261 ].…”

Section: Radium-223mentioning

confidence: 99%

Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The “Hopeful Eight”

et al. 2021

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Among all existing radionuclides, only a few are of interest for therapeutic applications and more specifically for targeted alpha therapy (TAT). From this selection, actinium-225, astatine-211, bismuth-212, bismuth-213, lead-212, radium-223, terbium-149 and thorium-227 are considered as the most suitable. Despite common general features, they all have their own physical characteristics that make them singular and so promising for TAT. These radionuclides were largely studied over the last two decades, leading to a better knowledge of their production process and chemical behavior, allowing for an increasing number of biological evaluations. The aim of this review is to summarize the main properties of these eight chosen radionuclides. An overview from their availability to the resulting clinical studies, by way of chemical design and preclinical studies is discussed.

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Radium-223 dichloride in prostate cancer: proof of principle for the use of targeted alpha treatment in clinical practice

Cited by 14 publications

References 46 publications

Practical considerations for quantitative clinical SPECT/CT imaging of alpha particle emitting radioisotopes

Practical considerations for quantitative clinical SPECT/CT imaging of alpha particle emitting radioisotopes

The role of dosimetry and biological effects in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study

Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The “Hopeful Eight”

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