Direct radiolabeling of methotrexate and methotrexate micelles with Tc-99m using QbD approach.

The aim of the work presented in this manuscript was to radiolabel methotrexate and prepare radiolabeled methotrexate micelles, an antifolate drug with Tc-99m using QbD approach. The radiolabeling was executed using the experimental design and the radiolabeled drug was further encapsulated in micelles. The authors are of the view that the radiolabeled MTX could be used to target the folate receptor overexpressing cancers such as the kidney, colorectal, breast, brain etc thereby opening newer possibilities to the theranostic applications of the formed conjugate.

Modification and Functionalization of Polymers for Targeting to Bone Cancer and Bone Regeneration.

Bone is one of the most complex, inaccessible body structures, responsible for calcium storage and haematopoiesis. The second highest cause of death across the world is cancer. Amongst all the types of cancers, bone cancer treatment modalities are limited due to the structural complexity and inaccessibility of bones. The worldwide incidence of bone diseases and bone defects due to cancer, infection, trauma, age-related bone degeneration is increasing. Currently different conventional therapies are available for bone cancer such as chemotherapy, surgery and radiotherapy, but they have several disadvantages associated with them. Nanomedicine is being extensively researched as viable therapeutics to mitigate drug resistance in cancer therapy and promote bone regeneration. Several natural polymers such as chitosan, dextran, alginate, hyaluronic acid, and synthetic polymers like polyglycolic acid, poly(lactic-co-glycolic acid), polycaprolactone are investigated for their application in nanomedicine for bone cancer treatment and bone regeneration. Nanocarriers have shown promising results in preclinical experimental studies. However, they still face a major drawback of inadequate targetability. The paper summarizes the status of research and the progress made so far in modifications and functionalization of natural polymers for improving their site specificity and targeting for effective treatment of bone cancer and enhancing bone regeneration.

One decade of 'Bench-to-Bedside' peptide receptor radionuclide therapy with indigenous [177Lu]Lu-DOTATATE obtained through 'Direct' neutron activation route: lessons learnt including practice evolution in an Indian setting.

The present treatise chronicles one decade of experience pertaining to clinical PRRT services in a large-volume tertiary cancer care centre in India delivering over 4,000 therapies, an exemplar of successful PRRT programme employing indigenous 177Lutetium production and resources. For the purpose of systematic discussion, we have sub-divided the communication into 3 specific parts: (a) Radiopharmaceutical aspects that describes 177Lutetium production through 'Direct' Neutron Activation Route and the subsequent radiolabeling procedures, (b) The specific clinical nuances and finer learning points (apart from the routine standard procedure) based upon clinical experience and how it has undergone practice evolution in our setting and (c) Dosimetry results with this indigenous product and radiation safety/health physics aspects involved in PRRT services. Initiated in 2010 at our centre, the PRRT programme is a perfect example of affordable quality health care delivery, with indigenous production of the radionuclide (177Lu) in the reactor and subsequent radiolabeling of the radiopharmaceutical ([177Lu]Lu-DOTATATE) at the hospital radiopharmacy unit of the centre, which enabled catering to the needs of a large number of patients of progressive, metastatic and advanced Neuroendocrine Neoplasms (NENs) and related malignancies.

Formulation and evaluation of novel micellar nanocarrier for nasal delivery of sumatriptan.

AIM: The investigation was aimed at designing a micellar nanocarrier of sumatriptan for nose-to-brain delivery and to identify the probable pathway of drug transport to the brain. MATERIALS & METHODS: Micellar nanocarriers were formulated using various safe and acceptable excipients. Optimized formulation was characterized for particle size by multiangle dynamic light scattering, small-angle neutron scattering and cryo-transmission electron microscopy. (99m)Tc was used as a radiolabeling agent to radiolabel sumatriptan for in vivo studies. RESULTS: Various characterization studies demonstrated the nanometric, homogenous and spherical nature of the developed micellar nanocarrier. Biodistribution and autoradiography studies in rats showed a significantly higher brain uptake of sumatriptan micellar nanocarrier as compared with sumatriptan solution. CONCLUSION: Preliminary investigations in rats indicated the potential of the developed micellar nanocarrier for nose-to-brain delivery of sumatriptan. These investigations in lower animals provided an excellent lead to further evaluate the formulation in higher animals and finally in clinical settings.

Micellar nanocarriers: potential nose-to-brain delivery of zolmitriptan as novel migraine therapy.

PURPOSE: The investigation was aimed at developing micellar nanocarriers for nose-to-brain delivery of zolmitriptan with the objective to investigate the pathway involved in the drug transport. METHODS: The micellar nanocarrier was successfully formulated and characterized for particle size and shape by multi-angle dynamic light scattering, small angle neutron scattering and cryo-transmission electron microscopy. Toxicity and biodistribution studies were carried out in rat. The distribution of the nasally administered labeled micellar nanocarrier in various regions of the rat brain was determined using the brain localization and autoradiography studies. RESULTS: Micellar nanocarrier of zolmitriptan, with size of around 23 nm, was successfully formulated. The spherical nature of the nanocarrier was confirmed using DLS, SANS and cryo-TEM. Toxicity studies indicated the safety for administration in the nasal cavity. In vivo biodistribution studies indicated the superiority of the developed nanocarrier for brain targeting when compared with the intravenous and nasal solutions of the drug. Brain localization and autoradiography studies illustrated the distribution of the drug in various regions of the brain and revealed a possible nose-to-brain transport pathway for the labeled drug. CONCLUSION: The investigation indicated the potential of the developed nanocarrier as an effective new-generation vehicle for brain targeting of zolmitriptan.

Bronchoalveolar carcinoma of lung masquerading as iodine avid metastasis in a patient with minimally invasive follicular carcinoma of thyroid.

A 52-year-old man with follicular thyroid carcinoma was administered 182 mCi of radioiodine (I-131) a month after total thyroidectomy. Post-therapy scan revealed diffuse uptake of radioiodine in the apical left lung. CT-guided biopsy of this mass revealed mucinous bronchoalveolar carcinoma. Immunohistochemistry for thyroglobulin was negative. An FDG PET scan showed avid uptake in the lung mass. Surgery was ruled out, so he was given chemotherapy, without benefit. The lesion continued to show I-131 uptake even while on daily T3 substitution, suggesting that the mass was thyroid stimulating hormone-independent. Because the mass showed I-131 uptake and chemotherapy was not beneficial, it was decided to treat with I-131. He was continued on T3 substitution therapy and was given 209 mCi of I-131. Follow-up CT scan a few weeks later reported a 1-cm all round reduction of the mass. I-131 scan showed avid tracer uptake in the mass. This case suggests the possibility of this therapeutic option in nonthyroidal tumors that may concentrate radioiodine.