M.G.R. Rajan

Potential Role of Fdg Pet Imaging in Predicting Metastatic Potential and Assessment of Therapeutic Response to Neoadjuvant Chemotherapy in Ewing Sarcoma Family of Tumors

Aims and Objectives: The aim of this study was to retrospectively correlate FDG uptake in primary Ewing sarcoma family of tumors (ESFT) with tumor behavior, and to evaluate whether FDG PET can be used to predict response to neoadjuvant chemotherapy (NACT) in this patient group. Methods: Out of the total 54 patients of recently diagnosed ESFT who underwent pretreatment FDG PET imaging, group I included patients without metastasis at presentation (n = 34) and group II included those with metastasis at presentation (n = 20). Fourteen of these patients had undergone FDG PET after 4 cycles of induction chemotherapy and surgical resection of primary tumor. In this subgroup of 14 patients, maximum standardized uptake value (SUVmax) of primary tumor was estimated before and after 4 cycles of induction chemotherapy and was correlated with the histopathological response in terms of necrosis in the tumor specimen. Results: Mean SUVmax in the primary tumor in group I patients was 6.84 and in group II patients, it was 11.31. The difference between mean SUVmax of these 2 groups was significant by Wilcoxon test analysis, with P < 0.01. In group II patients, SUVmax in metastasis with maximum FDG uptake was consistently lower as compared with that of primary tumor. In subgroup of 14 patients, Pearson correlation analysis showed that percentage change in SUVmax of primary tumor correlated well with percentage necrosis on histopathological examination (P < 0.01). Conclusion: FDG uptake in primary ESFT reflected its metastatic potential and hence the aggressive behavior. The significant correlation between change in metabolic activity of the primary tumor and histopathological response after neoadjuvant chemotherapy suggests that FDG PET may be an ideal noninvasive method to assess tumor behavior and response to therapy in ESFT.

Radioprotective Effect of Ocimum sanctum and Amifostine on the Salivary Gland of Rats After Therapeutic Radioiodine Exposure

The current study investigated the radioprotective effect of Ocimum sanctum on the salivary gland of rats administered radioiodine ((131)I) and compared its efficacy with a known radioprotectant, amifostine. The experimental rats were divided in four groups and sacrificed in three different batches at 1, 3, and 6 months of time interval after 18.5 MBq/100g (i.p.) (131)I exposure. Six months duration batch received (131)I exposure twice with the gap of 3 months. Two groups of experimental rats were presupplemented with O. sanctum (40 mg/kg for 5 days, orally) and amifostine (200 mg/kg, s.c) before (131)I exposure separately. Increased Technetium-99m-pertechnetate ((99m)TcO(4)(-)) uptake at 30 minutes post injection in salivary glands of only (131)I exposed rats may imply delay in clearance at 6 months of exposure in comparison to their counterparts sacrificed at 1 month. Parotid gland histology showed atrophy with lipomatosis in only (131)I exposed rats at 3 and 6 months of duration. O. sanctum and amifostine presupplemented and subsequently exposed to (131)I rats at 3 and 6 months duration exhibited comparable histopathology with controls. Our study indicates possible radioprotective effect of O. sanctum and amifostine against high-dose (131)I exposure.

'Reverse discordance' between 68Ga-DOTA-NOC PET/CT and 177Lu-DOTA-TATE posttherapy scan: the plausible explanations and its implications for high-dose therapy with radiolabeled somatostatin receptor analogs.

In this technical note, an unusual discordance between diagnostic and posttherapeutic scan resulting from the use of different somatostatin receptor ligands in two settings is described. Such observation, we believe, is multifactorial, but most importantly arises due to different receptor affinity profile of the ligands and different somatostatin receptor subtype expression in different tumors. It is important for the treating physician to be aware of this phenomenon that would aid in improving our understanding of complex ligand-receptor interactions in various somatostatin receptor-positive tumors with its possible implications for therapeutic decision making with radiolabeled somatostatin receptor analogues.

A Novel Folate-Targeted Nanoliposomal System of Doxorubicin for Cancer Targeting

Targeted drug delivery systems for cancer improves anti-tumor efficacy and reduces systemic toxicity by restricting availability of cytotoxic drugs within tumors. Targeting moieties, such as natural ligands (folic acid, transferrin, and biotin) which are overexpressed on tumors, have been used to enhance liposome-encapsulated drug accumulation within tumors and resulted in better control. In this report, we explored the scope of targeting ligand folic acid, which is incorporated in liposome systems using folic acid-modified cholesterol (CPF), enabled highly selective tumor-targeted delivery of liposome-encapsulated doxorubicin and resulted in increased cytotoxicity within tumors. Folate-tagged poloxamer-coated liposomes (FDL) were found to have significantly higher cellular uptake than conventional poloxamer-coated liposomes (DL), as confirmed by fluorometric analysis in B16F10 melanoma cells. Biodistribution study of the radiolabeled liposomal system indicated the significantly higher tumor uptake of FDL as compared to DL. Anti-tumor activity of FDL against murine B16F10 melanoma tumor-bearing mice revealed that FDL inhibited tumor growth more efficiently than the DL. Taken together, the results demonstrated the significant potential of the folate-conjugated nanoliposomal system for drug delivery to tumors.

Renal metastases from thyroid carcinoma.

We are writing regarding a recent article entitled ‘‘Renal Metastasis from Hurthle Cell Thyroid Carcinoma and Its Evaluation with Hybrid Imaging’’ by Djekidel et al. (1). We agree with the authors’ point regarding the rarity of renal involvement from primary cancers of the thyroid. In our recently accepted article, however, a literature search revealed that renal metastases from a primary thyroid cancer have been reported in about 20 patients to date (2). This is contrary to the authors’ claim that these metastases have been reported in only 10 patients. Another pertinent reference describing single photon emission computed tomography-computed tomography evidence for renal metastasis from follicular thyroid cancer should also be noted (3). Second, Marino et al. (4) have reported a rare case of renal metastasis from thyroid carcinoma that started as Hurthle cell adenoma and transformed into a carcinoma with a follicular appearance after 26 years. Hence, this may not be the first case of Hurthle cell cancer with renal metastases. Third, we were surprised to find that multiple lesions that showed F-18 fluorodeoxyglucose uptake were not thought to show iodine concentration. Perhaps, a small amount of abnormal uptake could have been missed on the radioiodine scan. In the literature and from our institutional experience of treating advance metastatic thyroid cancer, we find that many such lesions show both fluorodeoxyglucose and iodine avidity. Hence, they are amenable to administration of radioiodine therapy, in high doses of 200–250 mCi, with intent to palliate. Many such patients have dramatic symptomatic relief and good quality of life despite harboring multiple metastases.

Radiosynthesis and preclinical evaluation of [18F] 4-(2-fluoroethoxy)-2H-chromen-2-one as a novel myocardial perfusion imaging agent

Abstract Recently we developed [18F] 4-(2-fluoroethoxy)-2H-chromen-2-one as a novel 18F myocardial perfusion imaging radiotracer. It was synthesized in good radiochemical yield (>90%). The total time from radiosynthesis to its purification was less than 40 min, with excellent radiochemical purity (≥99%). It showed good stability over a period of 5 h at room temperature. The partition coefficient (log P) of radiotracer was found to be 2.70, suggesting the lipophilic nature of radiotracer. Ex vivo biodistribution study of radiotracer in normal Wistar rats for 30 min post-injection, demonstrated a good heart uptake (>1.3% ID/g) and favorable pharmacokinetics. Additionally, the radiotracer showed significant excretion (>11% ID) by liver, which is indicative of its rapid clearance. Further, in vivo biodistribution study of radiotracer in New Zealand White rabbit provided the clear PET/CT images of cardiomyocytes and myocardial perfusion. All these experimental findings suggest that [18F] 4-(2-fluoroethoxy)-2H-chromen-2-one could be used as a potential hit for myocardial perfusion imaging.

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.

Correlation between dose rate and physical factors of patients undergoing peptide receptor radionuclide therapy with (Lu-177)-DOTATATE

In peptide receptor radionuclide therapy (PRRNT) for the treatment of neuroendocrine tumors with (Lu-177)-DOTATATE, large variations in dose rate at 1 m from the patients body surface administered with same amount of Lu-177 activity are observed. The aim of this prospective study was to explain the cause of the variations and see if there is correlation between the dose rate per unit activity at 1 m distance from patients body surface in PRRNT with (Lu-177)-DOTATATE and physical factors such as height, weight, age, body surface area (BSA), body mass index (BMI), height/weight (H/W) ratio, and BSA/BMI ratio. From this study, it is observed that dose rate per unit activity at 1 m distance from patients body surface is significantly correlated with BMI, H/W ratio, and weight of the patients. Male and female patients data were also separately analyzed, and there was no statistically significant difference observed in these groups of patients. As BMI or weight of the patient is increases, dose rate per unit activity at 1 m distance from patients body surface decreases and as H/W ratio increases dose rate per unit activity at 1 m distance from patients body surface also increases. Moderate correlation was seen with BSA and BSA/BMI ratio of the patients. No correlation was seen with age and height of the patients. From this study, H/W ratio can be considered as a good parameter for correlating the dose rate and activity retained in the patients body. H/W ratio of patient affects the external dose measurement at 1 m from body surface immediately post-Lu-177 labeled PRRNT therapy. Thus, the study is important in formulating the regulatory criterion for discharge of patients after the treatment.