Internal dosimetry studies of 170Tm-EDTMP complex, as a bone pain palliation agent, in human tissues based on animal data.

Radiopharmaceuticals with therapeutic applications are designed to deliver high doses of radiation to target organs with minimizing unwanted radiation to healthy tissues. Owing to the potential of targeted radiotherapy to treat a wide range of malignancies, 170Tm -EDTMP was developed for possible therapeutic applications. This study describes absorbed dose prediction of 170Tm-EDTMP in human organs after animal injection which is determined via medical internal radiation dose (MIRD) and MCNP-4C code methods. It was estimated that a 1-MBq administration of 170Tm-EDTMP into the human body would result in an absorbed dose of 37.9 mGy (MIRD method) and 38.02 mGy (MCNP-4C code) in the bone surface after 60 days post injection. Highest and lowest difference between MIRD and MCNP results are for lung and bone surface respectively. Finally, the results show that there is a good agreement between MIRD method and MCNP-4C simulation code for absorbed dose estimation.

Safety and effectiveness of high-power thulium laser enucleation of the prostate in patients with glands larger than 80 mL.

BACKGROUND: The efficacy of thulium laser prostate enucleation (ThuLEP) for large prostates is unclear. This study aimed to explore the expanded utility of 150-200-W ThuLEP by studying patients with a large prostate (> 80 mL). METHODS: We retrospectively reviewed records of 125 patients with large prostate glands (> 80 mL) who underwent ThuLEP performed by a single surgeon from June 2012 to June 2016. The ThuLEP data from our previous pilot study were used as the control. Operative variables, patient profiles, preoperative and postoperative urine flow rates, prostate volume, and the international prostate symptom score (IPSS) were recorded and analyzed using Student's t-test, the z-test, and logistic regression analysis. RESULTS: Of 366 patients who underwent ThuLEP, 125 (34.15%) were enrolled. The ages and estimated prostate volumes were compared with those of the control. Overall, 39.2% underwent Foley placement and 4% received an anticoagulant agent preoperatively. Maximum urinary flow rates before and 3 and 12 months postoperatively were 9.93, 23.20, and 19.00 mL/s, respectively, which were generally equal to those of the control groups (P = 0.68, 0.18, 0.98, respectively). Preoperative and postoperative IPSSs were 27.09 and 7.35, respectively. The postoperative prostate-specific antigen was reduced by 85.59% in comparison to the preoperative level. The estimated prostate size was reduced by 74.17% postoperatively. The modified Clavien-Dindo classification system was used to identify the overall rate of complications, which was approximately 22.4%. The mortality rate was 0.8%. CONCLUSIONS: High-power ThuLEP is safe and effective for patients with large prostate glands (> 80 mL). Prostate enucleation using a high-power thulium laser is feasible for patients who exhibit contraindications for surgery.

Radiochemical studies, pre-clinical investigation and preliminary clinical evaluation of 170Tm-EDTMP prepared using in-house freeze-dried EDTMP kit.

The objective of the present work is to formulate 170Tm-EDTMP using an in-house freeze-dried EDTMP kit and evaluate its potential as a bone pain palliation agent. Patient dose of 170Tm-EDTMP was prepared with high radiochemical purity using the lyophilized kit at room temperature within 15min. Pre-clinical evaluation in normal Wistar rats revealed selective skeletal accumulation with extended retention. Preliminary clinical investigation in 8 patients with disseminated skeletal metastases exhibited selective uptake in the bone and retention therein for a long duration.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

Thulium-170-labeled microparticles for local radiotherapy: preliminary studies.

The present article describes the preparation, characterization, and biological evaluation of Thulium-170 ((170)Tm) [T1/2 = 128.4 days; Eßmax = 968 keV; Eγ = 84 keV (3.26%)] labeled tin oxide microparticles for its possible use in radiation synovectomy (RSV) of medium-sized joints. (170)Tm was produced by irradiation of natural thulium oxide target. 170Tm-labeled microparticles were synthesized with high yield and radionuclidic purity (> 99%) along with excellent in vitro stability by following a simple process. Particle sizes and morphology of the radiolabeled particles were examined by light microscope, dynamic light scattering, and transmission electron microscope and found to be of stable spherical morphology within the range of 1.4-3.2 µm. The preparation was injected into the knee joints of healthy Beagle dogs intraarticularly for biological studies. Serial whole-body and regional images were taken by single-photon-emission computed tomography (SPECT) and SPECT-CT cameras up to 9 months postadministration, which showed very low leakage (< 8% of I.D.) of the instilled particles. The majority of leaked radiocolloid particles were found in inguinal lymph nodes during the 9 months of follow-up. All the animals tolerated the treatment well; the compound did not show any possible radiotoxicological effect. These preliminary studies showed that 170Tm-labeled microparticles could be a promising nontoxic and effective radiopharmaceutical for RSV applications or later local antitumor therapy.

[Greenlight photoselective vaporization prostatectomy versus thulium laser vaporesection of the prostate for aged high-risk BPH patients with the prostate heavier than 80 g].

OBJECTIVE: To compare the effects of greenlight photoselective vaporization prostatectomy (PVP) and thulium laser vaporesection of the prostate (TmLRP) in the treatment of aged high-risk BPH patients with the prostate weighing > 80 g. METHODS: We included in this study 118 high-risk BPH patients aged 62-96 (mean 76) years with the prostate heavier than 80 g, 82 treated by PVP and the other 36 by TmLRP. Then we compared the operation time, intraoperative bleeding, complications, short-term effectiveness, and surgical cost between the two groups. RESULTS: All the patients tided over the perioperative period without blood transfusion and serious complications. The mean operation time, postoperative bladder irrigation time and surgical cost were significantly less in the TmLRP than in the PVP group (P < 0.05). Both the procedures remarkably improved the international prostatic symptom score (IPSS), quality of life (QOL), post void residual urine (PVR) and Qmax of the patients (P < 0.05), but with no significant differences between the two groups (P > 0.05). CONCLUSION: Both PVP and TmLRP are effective and safe for the treatment of aged high-risk BPH patients with the prostate heavier than 80 g, but the latter is superior for its shorter operation time and lower surgical cost.

[Whole-body retention studies of 167Tm-citrate.--Estimation of radiation dose to human from 167Tm-citrate--(author's transl)].

For the purpose of calculating absorbed dose to humans from 167Tm-citrate, the whole-body retention studies using 5 rats were carried out. Up to 40 days following intravenous injection of 167Tm-citrate, the whole-body counts were monitored with a animal counter. The whole-body retention curve was obtained with three exponentaial components. Namely, the 26% of the injected 167 Tm-citrate had a biological half-time of 3.4 hours, 12.5% had a biological half-time of 99 hours and 61.5% had a biological half-time of 106 days. These results indicate, that three components consist of the rapid clearance from the kidneys, the retention in the liver and other soft tissues with relatively long half-time and the retention in the bones with long half-time. Based on these biological data and the MIRD Committee method, the average dose estimates to the bone and whole-body from intravenous administration of 1 mCi 167Tm-citrate were 7.08 rads and 1.28 rads, respectively.