| 1. |
- Dewaraja, Yuni K., et al.
(author)
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MIRD Pamphlet No. 24: Guidelines for Quantitative I-131 SPECT in Dosimetry Applications
- 2013
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 54:12, s. 2182-2188
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Journal article (peer-reviewed)abstract
- The reliability of radiation dose estimates in internal radionuclide therapy is directly related to the accuracy of activity estimates obtained at each imaging time point. The recently published MIRD pamphlet no. 23 provided a general overview of quantitative SPECT imaging for dosimetry. The present document is the first in a series of isotope-specific guidelines that will follow MIRD 23 and focuses on one of the most commonly used therapeutic radionuclides, I-131. The purpose of this document is to provide guidance on the development of protocols for quantitative I-131 SPECT in radionuclide therapy applications that require regional (normal organs, lesions) and 3-dimensional dosimetry.
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| 2. |
- Taldone, Tony, et al.
(author)
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Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71
- 2016
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In: Journal of labelled compounds & radiopharmaceuticals. - : WILEY-BLACKWELL. - 0362-4803 .- 1099-1344. ; 59:3, s. 129-132
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Journal article (peer-reviewed)abstract
- Heat shock protein 90 (Hsp90) is an ATP dependent molecular chaperone protein whose function is critical for maintaining several key proteins involved in survival and proliferation of cancer cells. PU-H71 (1), is a potent purine-scaffold based ATP pocket binding Hsp90 inhibitor which has been shown to have potent activity in a broad range of in vivo cancer models and is currently in Phase I clinical trials in patients with advanced solid malignancies, lymphomas, and myeloproliferative neoplasms. In this report, we describe the radiosynthesis of [I-124]-PU-H71(5); this was synthesized from the corresponding Boc-protected stannane precursor 3 by iododestannylation with [I-124]-NaI using chloramine-T as an oxidant for 2min, followed by Boc deprotection with 6 N HCl at 50 degrees C for 30min to yield the final compound. The final product 5 was purified using HPLC and was isolated with an overall yield of 55 +/- 6% (n=6, isolated) from 3, and >98% purity and an average specific activity of 980mCi/mu mol. Our report sets the stage for the introduction of [I-124]-PU-H71 as a potential non-invasive probe for understanding biodistribution and pharmacokinetics of PU-H71 in living subjects using positron emission tomography imaging.
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| 3. |
- Thorek, Daniel L J, et al.
(author)
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Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models.
- 2015
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In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016. ; 93:2, s. 444-453
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Journal article (peer-reviewed)abstract
- To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry.
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| 4. |
- Veach, Darren R., et al.
(author)
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PSA-Targeted Alpha-, Beta-, and Positron-emitting immunotheranostics in murine prostate cancer models and nonhuman primates
- 2021
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In: Clinical Cancer Research. - 1078-0432. ; 27:7, s. 2050-2060
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Journal article (peer-reviewed)abstract
- Purpose: Most patients with prostate cancer treated with androgen receptor (AR) signaling inhibitors develop therapeutic resistance due to restoration of AR functionality. Thus, there is a critical need for novel treatment approaches. Here we investigate the theranostic potential of hu5A10, a humanized mAb specifically targeting free PSA (KLK3). Experimental Design: LNCaP-AR (LNCaP with overexpression of wildtype AR) xenografts (NSG mice) and KLK3-Hi- Myc transgenic mice were imaged with 89Zr- or treated with 90Y- or 225Ac-labeled hu5A10; biodistribution and subcellular localization were analyzed by gamma counting, PET, autoradiography, and microscopy. Therapeutic efficacy of [225Ac]hu5A10 and [90Y]hu5A10 in LNCaP-AR tumors was assessed by tumor volume measurements, time to nadir (TTN), time to progression (TTP), and survival. Pharmacokinetics of [89Zr]hu5A10 in nonhuman primates (NHP) were determined using PET. Results: Biodistribution of radiolabeled hu5A10 constructs was comparable in different mouse models. Specific tumor uptake increased over time and correlated with PSA expression. Treatment with [90Y]/[225Ac]hu5A10 effectively reduced tumor burden and prolonged survival (P ≤ 0.0054). Effects of [90Y]hu5A10 were more immediate than [225Ac]hu5A10 (TTN, P < 0.0001) but less sustained (TTP, P < 0.0001). Complete responses were observed in 7 of 18 [225Ac]hu5A10 and 1 of 9 mice [90Y]hu5A10. Pharmacokinetics of [89Zr]hu5A10 were consistent between NHPs and comparable with those in mice. [89Zr]hu5A10-PET visualized the NHP-prostate over the 2-week observation period. Conclusions: We present a complete preclinical evaluation of radiolabeled hu5A10 in mouse prostate cancer models and NHPs, and establish hu5A10 as a new theranostic agent that allows highly specific and effective downstream targeting of AR in PSAexpressing tissue. Our data support the clinical translation of radiolabeled hu5A10 for treating prostate cancer.
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