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Intrinsically radiolabeled inorganic nanoparticles represent a new paradigm in personalized treatment of cancer. To minimize their potential side effects for future clinical translation, it is desirable to explore biocompatible materials for synthesis of the cancer-targeting nanoparticles. In this study, we report a unique human serum albumin (HSA)-mediated biomineralization process for synthesis of intrinsically radiolabeled [177Lu]­Lu2O3 nanoparticles entrapped in a protein scaffold ([177Lu]­Lu2O3-HSA nanocomposite). Various instrumental techniques such as X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), transmission electron microscopy (TEM), etc. were utilized for characterization of as-synthesized nonradioactive nanoparticles. The intrinsically 177Lu-labeled nanoparticles demonstrated excellent in vitro and in vivo stability in preclinical settings. Cell binding and toxicity studies demonstrated the binding affinity and specificity of the intrinsically radiolabeled nanoparticles toward melanoma (B16F10) cells for use as a radiotherapeutic agent. Biodistribution studies demonstrated rapid and enhanced accumulation of the radiolabeled nanoparticles in the tumor (11.7 ± 2.1%ID/g at 4 h post-injection) with significant retention up to 7 days. The therapeutic efficacy of the [177Lu]­Lu2O3–HSA nanocomposite was demonstrated by tumor regression studies performed over a period of 21 days. The encouraging results obtained in this study demonstrate the potential of the [177Lu]­Lu2O3–HSA nanocomposite for clinical translation. This strategy will also facilitate the synthesis of other radiolabeled biocompatible nanoparticles for use in cancer theranostics.

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Purpose. To improve success of in vitro fertilization (IVF), assisted reproductive technology (ART) experts addressed four questions. What is optimum oocytes number leading to highest live birth rate (LBR)? Are cohort size and embryo quality correlated? Does gonadotropin type affect oocyte yield? Should “freeze-all” policy be adopted in cycles with progesterone >1.5 ng/mL on day of human chorionic gonadotropin (hCG) administration? Methods. Electronic database search included ten studies on which panel gave opinions for improving current practice in controlled ovarian stimulation for ART. Results. Strong association existed between retrieved oocytes number (RON) and LBRs. RON impacted likelihood of ovarian hyperstimulation syndrome (OHSS). Embryo euploidy decreased with age, not with cohort size. Progesterone > 1.5 ng/dL did not impair cycle outcomes in patients with high cohorts and showed disparate results on day of hCG administration. Conclusions. Ovarian stimulation should be designed to retrieve 10–15 oocytes/treatment. Accurate dosage, gonadotropin type, should be selected as per prediction markers of ovarian response. Gonadotropin-releasing hormone (GnRH) antagonist based protocols are advised to avoid OHSS. Cumulative pregnancy rate was most relevant pregnancy endpoint in ART. Cycles with serum progesterone ≥1.5 ng/dL on day of hCG administration should not adopt “freeze-all” policy. Further research is needed due to lack of data availability on progesterone threshold or index.