Gamma Camera Imaging of Platinum in Tumours and Tissues of Patients after Administration of<sup>191</sup>Pt-Cisplatin

Areberg, Sven Björkman Johan

doi:10.1080/028418699431654

Cited by 32 publications

(6 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, platinum levels are highest in liver in rats (34), mice (35), and are consistently higher than those observed in other organs in humans (36). The high liver uptake of platinum in humans has been confirmed using gamma camera imaging in patients with cancer following a dose of 191 Pt-cisplatin (37). …”

Section: Discussionmentioning

confidence: 96%

Modulation of OATP1B-Type Transporter Function Alters Cellular Uptake and Disposition of Platinum Chemotherapeutics

Lancaster

Sprowl

Walker

et al. 2013

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Expression of the human organic anion transporting polypeptides OATP1B1 and OATP1B3 have been previously believed to be restricted to hepatocytes. Here we demonstrate that the gene encoding OATP1B3, but not OATP1B1, is abundantly expressed in multiple human solid tumors that include hepatocellular, lung, and ovarian carcinomas. Surprisingly, OATP1B3 expression in a panel of 60 human tumor cell lines was linked with sensitivity to multiple cytotoxic agents, including the platinum anticancer drugs cisplatin, carboplatin, and oxaliplatin. In addition, overexpression of OATP1B3 in mammalian cells increased cellular accumulation of platinum agents and decreased cell survival. In mice with a targeted disruption of the ortholog transporter Oatp1b2, the liver-to-plasma ratio of cisplatin was significantly reduced compared with wildtype mice, without concurrent changes in expression profiles of other transporter genes. Our findings indicate an unexpected role for tumoral and host OATP1B-type carriers in the toxicity and disposition of platinum anticancer drugs, and may provide a foundation for understanding the extensive interindividual pharmacodynamic variability seen with these drugs in patients.

show abstract

Section: Discussionmentioning

confidence: 96%

Modulation of OATP1B-Type Transporter Function Alters Cellular Uptake and Disposition of Platinum Chemotherapeutics

Lancaster

Sprowl

Walker

et al. 2013

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…191 Pt decays with a half-life of 2.8 days by EC, producing 17.8 KeV of AEs per decay (and 273 KeV/decay in γ-photons) (Table 1 , Eckerman and Endo 2008). Areberg et al produced 191 Pt by proton irradiation (75–65 MeV) of gold foil [ 197 Au(p,2p,5n) 191 Pt, 197 Au(p,p6n) 191 Au➔ 191 Pt, 197 Au(p,7n) 191 Hg➔ 191 Au➔ 191 Pt] and synthesised 191 Pt-cisplatin (Areberg et al 1999). The in vitro cytotoxicity of 191 Pt-cisplatin was assessed at increasing specific activities of 0–167 MBq/mg (0–20 μg/mL) on ME180 human cervical carcinoma cells to determine the IC 50 values (Areberg et al 2000) which is the concentration required to inhibit cell growth by 50%.…”

Section: Preclinical Studiesmentioning

confidence: 99%

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

266

207

View full text Add to dashboard Cite

Background: Auger electrons (AEs) are very low energy electrons that are emitted by radionuclides that decay by electron capture (e.g. 111 In, 67 Ga, 99m Tc, 195m Pt, 125 I and 123 I). This energy is deposited over nanometre-micrometre distances, resulting in high linear energy transfer (LET) that is potent for causing lethal damage in cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for treatment of cancer. In this review, we describe the radiobiological properties of AEs, their radiation dosimetry, radiolabelling methods, and preclinical and clinical studies that have been performed to investigate AEs for cancer treatment. Results: AEs are most lethal to cancer cells when emitted near the cell nucleus and especially when incorporated into DNA (e.g. 125 I-IUdR). AEs cause DNA damage both directly and indirectly via water radiolysis. AEs can also kill targeted cancer cells by damaging the cell membrane, and kill non-targeted cells through a cross-dose or bystander effect. The radiation dosimetry of AEs considers both organ doses and cellular doses. The Medical Internal Radiation Dose (MIRD) schema may be applied. Radiolabelling methods for complexing AE-emitters to biomolecules (antibodies and peptides) and nanoparticles include radioiodination (125 I and 123 I) or radiometal chelation (111 In, 67 Ga, 99m Tc). Cancer cells exposed in vitro to AE-emitting radiotherapeutic agents exhibit decreased clonogenic survival correlated at least in part with unrepaired DNA double-strand breaks (DSBs) detected by immunofluorescence for γH2AX, and chromosomal aberrations. Preclinical studies of AE-emitting radiotherapeutic agents have shown strong tumour growth inhibition in vivo in tumour xenograft mouse models. Minimal normal tissue toxicity was found due to the restricted toxicity of AEs mostly on tumour cells targeted by the radiotherapeutic agents. Clinical studies of AEs for cancer treatment have been limited but some encouraging results were obtained in early studies using 111 In-DTPAoctreotide and 125 I-IUdR, in which tumour remissions were achieved in several patients at administered amounts that caused low normal tissue toxicity, as well as promising improvements in the survival of glioblastoma patients with 125 I-mAb 425, with minimal normal tissue toxicity. Conclusions: Proof-of-principle for AE radiotherapy of cancer has been shown preclinically, and clinically in a limited number of studies. The recent introduction of many biologically-targeted therapies for cancer creates new opportunities to design novel AE-emitting agents for cancer treatment. Pierre Auger did not conceive of the application of AEs for targeted cancer treatment, but this is a tremendously exciting future that we and many other scientists in this field envision.

show abstract

“…XFCT has also been proposed as a method for monitoring the uptake of chemotherapy drug Cisplatin, based on the detection of the platinum atom in the drug [8]. Concentrations of 5–40 µg/mL (0.0005%–0.004%) have been measured in cancer patients undergoing Cisplatin chemotherapy [14], [15]. Thus the sensitivity must be greatly improved in order to make XFCT useful for in vivo molecular imaging applications.…”

Section: Introductionmentioning

confidence: 99%

Order of Magnitude Sensitivity Increase in X-ray Fluorescence Computed Tomography (XFCT) Imaging With an Optimized Spectro-Spatial Detector Configuration: Theory and Simulation

Ahmad

Bazalova

Xiang

et al. 2014

IEEE Trans. Med. Imaging

View full text Add to dashboard Cite

The purpose of this study was to increase the sensitivity of XFCT imaging by optimizing the data acquisition geometry for reduced scatter X-rays. The placement of detectors and detector energy window were chosen to minimize scatter X-rays. We performed both theoretical calculations and Monte Carlo simulations of this optimized detector configuration on a mouse-sized phantom containing various gold concentrations. The sensitivity limits were determined for three different X-ray spectra: a monoenergetic source, a Gaussian source, and a conventional X-ray tube source. Scatter X-rays were minimized using a backscatter detector orientation (scatter direction > 110° to the primary X-ray beam). The optimized configuration simultaneously reduced the number of detectors and improved the image signal-to-noise ratio. The sensitivity of the optimized configuration was 10 µg/mL (10 pM) at 2 mGy dose with the mono-energetic source, which is an order of magnitude improvement over the unoptimized configuration (102 pM without the optimization). Similar improvements were seen with the Gaussian spectrum source and conventional X-ray tube source. The optimization improvements were predicted in the theoretical model and also demonstrated in simulations. The sensitivity of XFCT imaging can be enhanced by an order of magnitude with the data acquisition optimization, greatly enhancing the potential of this modality for future use in clinical molecular imaging.

show abstract

Gamma Camera Imaging of Platinum in Tumours and Tissues of Patients after Administration of¹⁹¹Pt-Cisplatin

Cited by 32 publications

References 18 publications

Modulation of OATP1B-Type Transporter Function Alters Cellular Uptake and Disposition of Platinum Chemotherapeutics

Modulation of OATP1B-Type Transporter Function Alters Cellular Uptake and Disposition of Platinum Chemotherapeutics

Auger electrons for cancer therapy – a review

Order of Magnitude Sensitivity Increase in X-ray Fluorescence Computed Tomography (XFCT) Imaging With an Optimized Spectro-Spatial Detector Configuration: Theory and Simulation

Contact Info

Product

Resources

About

Gamma Camera Imaging of Platinum in Tumours and Tissues of Patients after Administration of191Pt-Cisplatin

Cited by 32 publications

References 18 publications

Modulation of OATP1B-Type Transporter Function Alters Cellular Uptake and Disposition of Platinum Chemotherapeutics

Modulation of OATP1B-Type Transporter Function Alters Cellular Uptake and Disposition of Platinum Chemotherapeutics

Auger electrons for cancer therapy – a review

Order of Magnitude Sensitivity Increase in X-ray Fluorescence Computed Tomography (XFCT) Imaging With an Optimized Spectro-Spatial Detector Configuration: Theory and Simulation

Contact Info

Product

Resources

About

Gamma Camera Imaging of Platinum in Tumours and Tissues of Patients after Administration of¹⁹¹Pt-Cisplatin