Preparation and biological study of [68]Ga-DOTA-alendronate

Objective[s]: In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA-conjugated alendronate [DOTA-ALN] was synthesized and evaluated after labeling with gallium-68 [[68]Ga]

Methods: DOTA-ALN was synthesized and characterized, followed by [68]Ga-DOTA-ALN preparation, using DOTA-ALN and [68]GaCl[3] [pH: 4-5] at 92-95°C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation, biodistribution studies, and imaging were performed on the developed agent in normal rats

Results: The complex was prepared with high radiochemical purity [>99% as depicted by radio thin-layer chromatography; specific activity: 310-320 GBq/mmol] after solid phase purification and was stabilized for up to 90 min with a logP value of -2.91. Maximum ligand binding [65%] was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low [<1%] at 30 min after the injection. The data were also confirmed by sequential imaging at 30-90 min following the intravenous injection

Conclusion: The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors

Geriatric pain management, pharmacological and nonpharmacological considerations

Persistent pain is prevalent in the elderly population, although it is not an inevitable part of aging. It is important to understand how to manage pain effectively in old age, particularly because an increasing number of individuals are becoming older, or living longer. Several problems, less common in younger adults, may complicate the treatment of pain. An accurate pain assessment is required for the most efficient strategy of pain treatment. Challenges to an effective pain assessment include: pain underreporting by patients, atypical manifestations of pain in elderly, age-associated pharmacodynamic and pharmacokinetic changes to specific drugs, other general age-related changes, and misconceptions about tolerance or addiction to opioids. However, physicians are able to provide geriatric patients with appropriate analgesia by using comprehensive assessment involving a multidisciplinary approach, and the appropriate use of various treatment modalities.

Development of [111]In-labeled porphyrins for SPECT imaging

The aim of this research was the development of [111]In-labeled porphyrins as possible radiopharmaceuticals for the imaging of tumors. Ligands, 5, 10, 15, 20-tetrakis [3, 5-dihydroxyphenyl] porphyrin] [TDHPP], 5, 10, 15, 20-tetrakis [4-hydroxyphenyl] porphyrin [THPP] and 5, 10, 15, 20-tetrakis [3,4-dimethoxyphenyl] porphyrin] [TDMPP] were labeled with [111]InCl3 [produced from proton bombardment of natCd target] in 60 min at 80[degree sign]C. Quality control of labeled compounds was performed via RTLC and HPLC followed by stability studies in final formulation and presence of human serum at 37[degree sign]C for 48 h as well as partition coefficient determination. The biodistribution studies performed using tissue dissection and SPECT imaging up to 24h. The complexes were prepared with >99% radiochemical purity [HPLC and RTLC], high stability in 48h. Partition coefficients [calculated as log P] for [111]In-TDHPP, [111]In-THPP and [111]In-TDMPP were 0.88, 0.8 and 1.63 respectively. Due to urinary excretion with fast clearance for [111]In-TDMPP, this complex is probably a suitable candidate for considering as a possible tumor imaging agent

Dysplasia epiphysealis hemimelica [trevor syndrome] of talus in a 21-year old woman; case report

Dysplasia epiphysealis hemimelica is a rare nonhereditary epiphyseal disease that mimics synovial chondromatosis and osteochondroma of the joints. The disease mainly involves long bones of the lower extremities and tarsal bones. Herein we report 21-year old woman who presented with pain and limited range of ankle motion, who underwent surgical excision of talus exostosis after preoperative imaging and careful planning, after that she was discharged and her problem improved and she have no problem in three year follow up .pathologic examination of specimen confirm the diagnosis

Production and quality control of [67Ga]-DOTA-trastuzumab for radioimmunoscintigraphy

Breast cancer radioimmunoscintigraphy targeting HER2/neu expression is a growing field of work in nuclear medicine research. In this study, trastuzumab was successively labeled with [[67]Ga] GaCl3 after conjugation with DOTA-NHS-ester. The conjugates were purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated and total concentration was determined by spectrophotometric method. DOTA-Trastuzumab was labeled with [67]Ga. Radiochemical purity, integrity of protein after radiolabeling and stability of [67]Ga-DOTA-Trastuzumab were determined followed by biodistribution studies in wild-type rats [30 +/- 5.5 micro Ci, 2, 4 and 24 h p.i.]. The radioimmunoconjugate was prepared with a radiochemical purity of higher than 95% [RTLC]. The average chelate to antibody ratio [c/a] for the conjugate used in this study was 5.8:1. The final compound was stable in presence of PBS at 37[degree sign]C and room temperature. The sample was showed to have similar patterns of migration in the gel electrophoresis similar to the native protein. The accumulation of the radiolabeled antibody in liver, spleen, kidney, heart and other tissues demonstrates. [67]Ga-DOTA-Trastuzumab was prepared as a surrogate for important clinically applicable radionuclides used in SPECT and PET including In-111 and Cu-64 as a model of radiolabeling. It is also a potential compound for molecular imaging of SPECT for diagnosis and treatment studies and follow-up of HER2 expression in oncology

Production, quality control and biological evaluation of [153] Sm-TTHMP as a possible bone palliation agent

Various bone palliative therapeutic agents have been developed and widely used for bone metastasis such as [153]Sm-EDTMP. In this study, production, quality control and biodistribution studies of a newly developed therapeutic compound have been presented followed by imaging studies in wild-type rodents. [153]Sm-TTHMP was prepared starting from [153]Sm-SmCl[3], prepared by neutron activation of an enriched [152]Sm sample [purity >98%], and in-house synthesized TTHMP in 1h at 25[degree sign] C followed by stability tests, partition coefficient determination and biodistribution studies of in wild-type rodents using scarification and SPECT imaging. The radiolabled Sm complex was prepared in high radiochemical purity [>99%, ITLC] and specific activity of 278 GBq/mmol and demonstrated significant ability at 4, 25 and 37 [degree sign] C [in presence of human serum]. Initial biodistribution data showed significant bone accumulation of the tracer in 48h. [153]Sm-TTHMP can be a potential candidate for bone pain palliation therapy in skeletal metastases, although further biological studies in other mammals is still needed

Mucopolysaccharidoses: anesthetic considerations and clinical manifestations

Mucopolysaccharidosis [MPS] is a group of genetic disorders that presents challenges during anesthetic care and in particular difficulty with airway management. Patients should be managed by experienced anesthesiologists at centers that are familiar with these types of conditions. Rarely encountered disease states have been identified as important topics in the continuing education of clinical anesthesiologists. This review will define MPS, describe the pathophysiology of MPS, describe how patients with this rare lysosomal storage disorders have dysfunction of tissues, cite the incidence of MPS, list the clinical manifestations and specific problems associated with the administration of anesthesia to patients with MPS, present treatment options for patients with MPS, define appropriate preoperative evaluation and perioperative management of these patients, including, to anticipate potential postoperative airway problems

Red grain botryomycosis due to Staphylococcus aureus - A novel case report.

Staphylococcus aureus and some other bacteria are known to cause botryomycosis. These bacteria are known to produce yellowish-white soft grains. Only Actinomadura pelletieri is known to produce red grains. We report here a case of an intensely inflammatory type of botryomycosis. A 35-year-old male labourer presented with swelling, redness and multiple sinuses on his foot, of eight months duration. The purulent discharge contained bright red coloured grains, 0.5 to 1 mm in size, which were round to oval in shape. Gram-positive cocci were demonstrated in crushed granules and tissue sections. Culture yielded pure and heavy growth of Staphylococcus aureus . He responded very well to cefazolin. There is no other report of such red grain botryomycosis due to Staphylococcus aureus , available in literature. This is first case report of its kind in world literature.

Evaluation of [[67]Ga] citrate in the detection of various microorganism infections in animal models

Gallium-67 citrate has been known as a good infection agent in nuclear medicine for decades. In this work the value of [67]Ga-citrate has been investigated in infected animal models using SPECT imaging at optimized/standardized conditions. The bacterial [Staphylococcus aureus; S.a. and Escherichia coli; E.c.] and fungal [Candidae albicans; C.a.] species from standard sources were cultured according to the standard procedures and wild-type NMRI rats were inoculated by the injection of 5x10[7] microorganisms [MO] into their thighs and animals incubated for infection site formation for 2 and 3 days followed by iv injection of freshly prepared [67]Ga-citrate [45-50 micro Ci] and SPECT imaging performed at 2, 4 and 24 hours post injection in parallel with control groups. In S.a.-infected rats [67]Ga-citrate demonstrated hot spot foci at all time intervals esp. 24h post injections in contrast with normal animal scans. In case of C.a., the infected animals also demonstrated significant accumulation foci being most significant after 24h. In E.c.-infected animals however weak positive scans were obtained even after 24 hours. Our animal models developed for the evaluation of new infection-targeting agents were successfully positive using [67]Ga scan. These models can also be used in the evaluation of newly developed antibiotics in animal models for in vivo studies. The efficacy of [67]Ga-scan in our microorganism infection models can be summarized as S.A.>C.a.>E.c.

Rheumatoid arthritis: current pharmacologic treatment and anesthetic considerations

A diagnosis of rheumatoid arthritis carries with it a lifelong progressive disease; however twenty percent of patients enjoy periods of partial to total remission. After remission, the disease will frequently plague previously unaffected joints. Life expectancy is reduced by an average of three to seven years. Complications of RA include vasculitis and amyloidosis affecting any vessel, including the aorta. Additionally, complications of therapy such as chronic NSAID use leading to GI bleeding and infections associated with long term steroid use, can add to the difficulties of the disease. The recent discovery and use of anticytokines and DMARDs has lead to greatly reduced symptomology associated with RA and greater patient comfort. Side effects of drugs should be well understood including the risk of bleeding from NSAIDs. Management and surgical intervention of problems that arise from this disease vary dramatically. The anesthesiologist must be aware of airway pathologies, pain management techniques, and available pharmacology parameters

Trucut needle biopsy - accuracy and sensitivity in diagnosis of breast cancer: a study at Ganga Ram Hospital

In this study 410 patients with palpable breast masses clinically suspected of being carcinoma breast presenting to the breast cancer OPD at Sir Ganga Ram Hospital Lahore, were selected and subjected to Trucut needle biopsy from September 2002 to September 2003. Malignancy was confirmed in 360 patients by Trucut needle biopsy. Complications were rare, however slight bruising was seen in only 2% of cases. Intraductal carcinoma was seen in 72.70% patients. Only 4 false negative results but no false positive observed. Accuracy rate was 92.55%. Sensitivity was 94.4%