Gurupad Bandopadhyaya

Samarium-153 ethylenediamine tetramethylene phosphonate therapy for bone pain palliation in skeletal metastases

BACKGROUND Systemic therapy with radionuclides may be used for the treatment of patients with painful skeletal metastases owing to its efficacy, low cost and low toxicity. Imported radionuclides for pain palliation, like Strontium-89 are expensive; particularly for developing countries. In the Indian scenario, Samarium-153 (Sm-153) is produced in our own reactors and as a result, it is readily available and economical. AIM We undertook this study to determine the efficacy and toxicity of single-dose Sm-153 ethylenediamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases. MATERIALS AND METHODS Eightysix patients with painful skeletal metastases from various primaries, were treated with Sm-153 EDTMP at a dose of 37 MBq/kg. The effects were evaluated according to change in visual analogue pain score, analgesic consumption, Karnofsky performance score, mobility score and blood count tests, conducted regularly for 16 weeks. STATISTICS Repeated measures analysis. RESULTS The overall response rates were 73%, while complete response was seen in 12.4%. Reduction in analgesic consumption with improvement in Karnofsky performance score and mobility score, was seen in all responders. Response rates were 80.3 and 80.5% in breast and prostate cancer, respectively. One case, each of Wilms tumor, ovarian cancer, germ cell tumor testis, multiple myeloma, primitive neuroectodermal tumor and oesophageal cancer, did not respond to therapy. No serious side-effects were noted, except for fall in white blood cell, platelet and haemoglobin counts, which gradually returned to normal levels by six-eight weeks. CONCLUSION Sm-153 EDTMP provided effective palliation in 73% patients with painful bone metastases: the major toxicity was temporary myelosuppression.

PLGA Nanoparticles for Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Novel Approach towards Reduction of Renal Radiation Dose

Background Peptide receptor radionuclide therapy (PRRT), employed for treatment of neuroendocrine tumors (NETs) is based on over-expression of Somatostatin Receptors (SSTRs) on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, 177Lu-DOTATATE loaded PLGA nanoparticles (NPs) were formulated in the present study, as a potential therapeutic model for NETs. Methodology and Findings DOTATATE was labeled with Lutetium-177 (177Lu) (labeling efficiency 98%; Rf∼0.8). Polyethylene Glycol (PEG) coated 177Lu-DOTATATE-PLGA NPs (50∶50 and 75∶25) formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated) and 303.8±67.2 and 494.3±71.8 nm (coated) for PLGA(50∶50) and PLGA(75∶25) respectively. Encapsulation efficiency (EE) and In-vitro release kinetics for uncoated and coated NPs of PLGA (50∶50 & 75∶25) were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated) and 65.385±5.67% & 58.495±5.35% (coated). NPs showed initial burst release between 16.64–21.65% with total 42.83–44.79% over 21days. The release increased with coating to 20.4–23.95% initially and 60.97–69.12% over 21days. In-vivo studies were done in rats injected with 177Lu-DOTATATE and 177Lu-DOTATATE-NP (uncoated and PEG-coated) by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With 177Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated 177Lu-DOTATATE-NP. The high liver uptake with uncoated 177Lu-DOTATATE-NP (13.68±3.08% ID/g), reduced to 7.20±2.04%ID/g (p = 0.02) with PEG coating. Conclusion PLGA NPs were easily formulated and modified for desired release properties. PLGA 50∶50 NPs were a more suitable delivery vehicle for 177Lu-DOTATATE than PLGA 75∶25 because of higher EE and slower release rate. Reduced renal retention of 177Lu-DOTATATE and reduced opsonisation strongly advocate the potential of 177Lu-DOTATATE-PLGA-PEG NPs to reduce radiation dose in PRRT.

Soft tissue uptake of Tc99m-MDP in acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is associated rarely with hypercalcemia. This may be due to elevated levels of parathyroid hormone-related peptide (PTHrP). We report a case of an 18-year-old female patient who was presented with a pathological fracture of left intertrochanteric region. Bone scintigraphy was consistent with features of hypercalcemia associated with metastatic calcification. A bone marrow biopsy led to the diagnosis of ALL. The mechanism of hypercalcemia in ALL, metastatic calcification and soft tissue uptake of bone seeking agents in this case are discussed in detail.

99mTc-DMSA (V) in Evaluation of Osteosarcoma: Comparative Studies with 18F-FDG PET/CT in Detection of Primary and Malignant Lesions

To evaluate the role of 99mTc-DMSA (V) and [18F]FDG PET-CT in management of patients with osteosarcoma, 22 patients were included in our study. All patients underwent both 99mTc-DMSA (V) and whole-body [18F]FDG PET-CT scans within an interval of 1 week. 555–740 MBq of 99mTc-DMSA (V) was injected i.v. the whole-body planar, SPECT images of primary site and chest were performed after 3-4 hours. [18F]FDG PET-CT images were obtained 60 minutes after i.v. injection of 370 MBq of F-18 FDG. Both FDG PET-CT (mean SUVmax = 7.1) and DMSA (V) scans showed abnormal uptake at primary site in all the 22 patients (100% sensitivity for both). Whole-body PET-CT detected metastasis in 11 pts (lung mets in 10 and lung + bone mets in 1 patient). Whole-body planar DMSA (V) and SPECT detected bone metastasis in one patient, lung mets in 7 patients and LN in 1 patient. HRCT of chest confirmed lung mets in 10 patients and inflammatory lesion in one patient. 7 patients positive for mets on DMSA (V) scan had higher uptake in lung lesions as compared to FDG uptake on PET-CT. Three patients who did not show any DMSA uptake had subcentimeter lung nodule. Resuts of both 99mTc-DMSA (V) (whole-body planar and SPECT imaging) and [18F]FDG PET-CT were comparable in evaluation of primary site lesions and metastatic lesions greater than 1 cm. Though 99mTc-DMSA (V) had higher uptake in the lesions as compared to [18F]FDG PET-CT, the only advantage [18F]FDG PET-CT had was that it could also detect subcentimeter lesions.

SPECT/CT in the Diagnosis of Skull Base Osteomyelitis

Skull base osteomyelitis is a potentially fatal disease. We demonstrate here the utility of SPECT/CT in diagnosing this entity, which was not obvious on a planar bone scan. A 99mTc MDP bone scan with SPECT/CT was carried out on a patient with clinically suspected skull base osteomyelitis. Findings were correlated with contrast-enhanced CT (CECT) and MRI. Planar images were equivocal, but SPECT/CT showed intense uptake in the body of sphenoid and petrous temporal bone as well as the atlas corresponding to irregular bone destruction on CT and MRI. These findings indicate that SPECT/CT may have an additional role beyond planar imaging in the detection of skull base osteomyelitis.

Tc-99m tetrofosmin uptake in male breast cancer.

Breast carcinoma occurs rarely in men. Its imaging by mammography is difficult because male breast tissue is normally small in volume and adequate compression is not possible, which is a prerequisite for performing mammography. The authors describe a 65-year-old man with a right breast mass in whom the result of fine-needle aspiration cytology was inconclusive. A mammogram was also noncontributory because adequate compression was not possible as the mass was tender. Tc-99m tetrofosmin scintimammography showed intense focal uptake in the right breast. Excision biopsy confirmed the diagnosis of breast carcinoma.

Paradigm shift in theranostics of neuroendocrine tumors: conceptual horizons of nanotechnology in nuclear medicine

We present a comprehensive review of Neuroendocrine Tumors (NET) and the current and developing imaging and therapeutic modalities for NET with emphasis on Nuclear Medicine modalities. Subsequently, nanotechnology and its emerging role in cancer management, especially NET, are discussed. The article is both educative and informative. The objective is to provide an insight into the developments made in nuclear medicine and nanotechnology towards management of NET, individually as well as combined together.