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Cherenkov luminescence imaging modality takes advantage of optical Cherenkov photons since this light could be used for photoactivation, photodynamic therapy, photothermal therapy, excited fluorophores, etc. The aim of this work is to experimentally determine 18F Cherenkov spectrum from 200 to 1050 nm. By Monte Carlo simulation in a mouse modeled, the number of absorbed photons and those ballistic and scattered that left the mouse were computed to determine its implications on optical dosimetry. An 18F-FDG source was used to measure the Cherenkov emission of 18F by placing it inside the 6" integrating sphere. Light was measured 100 times for two different activities with a Cherenkov spectrophotometer and all spectra with similar form and central moment were selected. In this group, the average Cherenkov spectrum was generated from 200 to 1050 nm, then the amount of Cherenkov photons emitted in the 200–1050-nm range was computed. The mouse body was set up in the MCLTmx code using an ellipsoidal figure, with dimensions and mass corresponding to the average size of a 10-to-12-weeks-old male mouse that is the optimal age for experimentation. A Cherenkov light (CL) isotropic point-source was also simulated; it was placed at the origin of the ellipsoid, moving on the y-axis from 0 to 1.2 cm in 0.2 cm increments. As a result, the Cherenkov spectra absorbed and leaving the ellipsoid were obtained. The average experimental Cherenkov spectrum of 18F for 200–1050 nm was obtained. 18F emits 3.28 photons per decay in 200–1050 nm range if the beta is emitted in a medium with a 1.33 refractive index, that corresponds to water. The number of photons per decay emerging from the ventral and dorsal sides of the murine model was computed by Monte Carlo Simulation. Preclinical dosimetry will be more accurately ascertained as the relation between activity in a target region and the amount of CL leaving a volume such as that of a mouse. On the other hand, adequate internal dosimetry will help to predict with greater certainty whether the energy deposited in a volume of interest will be able to induce therapeutic effects. [ABSTRACT FROM AUTHOR]

Actinium-225 and other alpha-particle-emitting radionuclides have shown high potential for cancer treatment. Reconstituted high-density lipoproteins (rHDL) specifically recognize the scavenger receptor B type I (SR-BI) overexpressed in several types of cancer cells. Furthermore, after rHDL-SR-BI recognition, the rHDL content is injected into the cell cytoplasm. This research aimed to prepare a targeted 225Ac-delivering nanosystem by encapsulating the radionuclide into rHDL nanoparticles. The synthesis of rHDL was performed in two steps using the microfluidic synthesis method for the subsequent encapsulation of 225Ac, previously complexed to a lipophilic molecule (225Ac-DOTA-benzene-p-SCN, CLog P = 3.42). The nanosystem (13 nm particle size) showed a radiochemical purity higher than 99% and stability in human serum. In vitro studies in HEP-G2 and PC-3 cancer cells (SR-BI positive) demonstrated that 225Ac was successfully internalized into the cytoplasm of cells, delivering high radiation doses to cell nuclei (107 Gy to PC-3 and 161 Gy to HEP-G2 nuclei at 24 h), resulting in a significant decrease in cell viability down to 3.22 ± 0.72% for the PC-3 and to 1.79 ± 0.23% for HEP-G2 at 192 h after 225Ac-rHDL treatment. After intratumoral 225Ac-rHDL administration in mice bearing HEP-G2 tumors, the biokinetic profile showed significant retention of radioactivity in the tumor masses (90.16 ± 2.52% of the injected activity), which generated ablative radiation doses (649 Gy/MBq). The results demonstrated adequate properties of rHDL as a stable carrier for selective deposition of 225Ac within cancer cells overexpressing SR-BI. The results obtained in this research justify further preclinical studies, designed to evaluate the therapeutic efficacy of the 225Ac-rHDL system for targeted alpha-particle therapy of tumors that overexpress the SR-BI receptor. [ABSTRACT FROM AUTHOR]

Although liposomal doxorubicin (LPD) is widely used for cancer treatment, knowledge concerning the toxicity induced by this drug in healthy organs and tissues is limited. LPD-induced toxicity studies relative to free doxorubicin (DOX) have focused on cardiotoxicity in tumor-bearing animals. On the other hand, the results on DOX-induced cardiotoxicity depending on gender are controversial. One of the manifestations of toxicity is tissue inflammation. 67Ga-citrate has been used for decades to assess inflammation in various pathologies. In this work, the ex vivo biodistribution of 67Ga-citrate is used to evaluate induced multi-organ toxicity in healthy 10-week-old male and female CD1 mice treated for 5 weeks with LPD. Toxicity in males, determined by 67Ga-citrate, was evident only in the target organs of liposomes (spleen, liver, kidneys, and lungs); the average weight loss was 11% and mortality was 14%. In female mice, 67Ga-citrate revealed a cytotoxic effect in practically all organs, the average weight loss was 37%, and the mortality after the last dose of LPD was 66%. These results confirm the usefulness of 67Ga-citrate and the importance of stratifying by sex in the toxicological evaluation of drugs. [ABSTRACT FROM AUTHOR]

The search for methods that identify early toxicity, induced by chemotherapy, is urgent. Changes in the biodistribution of radiopharmaceuticals could give information on early toxicity. Ten-week-old CD1 male mice were divided into four groups. Two groups were administered a weekly dose of 5 mg/kg of doxorubicin hydrochloride (DOX) for 5 weeks and the control groups were administered saline solution. One week after the end of treatment, the biodistribution of 18F-FDG and 67Ga-citrate were carried out, as was the quantification of plasma enzymes CK, CK-MB, LDH and AST. All enzymes were higher in the treated animals, but only significant (p < 0.05) in the case of CK-MB. 18F-FDG uptake increased in all organs of treated animals except retroperitoneal fat, being significant in spleen, brain, heart, liver, lung, kidney, and inguinal fat. 67Ga-citrate had a more complex pattern. The uptake in the DOX group was higher in spleen, lung, kidney, testes, and gonadal fat, it did not change in brain, heart, and liver, and it was lower in the rest of the organs. It only showed significant differences in lung and pancreas. A thorough discussion of the possible causes that produced the change in biodistributions of both radiopharmaceuticals is included. The pilot study showed that both radiopharmaceuticals could identify early multi-organ toxicity induced by DOX. Although 18F-FDG seems to be better, 67Ga-citrato should not be ruled out a priori. The detection of early toxicity would serve to adopt treatments that prevent its progression, thus improving patient's quality of life. [ABSTRACT FROM AUTHOR]