Direct radiolabeling of Folate with Tc-99m using QbD approach: A step closer to folate based diagnostic agent.

The aim of the presented work was to develop folate based radiolabeled compound intended to be used as diagnostic aid for the various folate-receptor overexpressing cancers eg. breast cancer, brain tumors, lung cancer etc. Folate was directly radiolabeled with Tc-99m using Quality-by-Design and encapsulated in micellar nanocarriers. The authors are of the view that the stable radiolabeled folate could be of potential diagnostic value in cancers overexpressing folate receptors thereby opening novel possibilities to diagnostic applications of radiolabeled folate. SUMMARY FOR TECHNICAL NOTES: Folic acid was directly radiolabeled with Tc-99m utilizing a quality by design approach. The experimental trials were designed using the Box-Behenken design with the concentration of drug, concentration of reducing agent and the incubation time as dependent variable and percent radiolabeling as the response for the same. The applied design in the method section was validated with a series of experiments and the percent labeling of the FA with Tc-99m was found to be around 94%. The radiolabeled compound was imperilled to stability evaluation by incubating the same with serum and physiological pH and the same was found to be stable at the end of 4h. On subjecting to DTPA challenge test, the compound displayed no change in the radiolabeling percentage thereby indicating the robustness of the formed Tc-99m-FA complex, The radiolabeled Tc-99m-FA was further encapsulated into micellar nanocarriers and the same were also found to be robust and stable.

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.

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.