The role of nuclear medicine in oncology

Nuclear Medicine offers screening methods for oncology such as bone and bone marrow scintigraphy. During the last two decades, special procedures have gained widespread application. This paper is centered around the “tumor-specific” radiopharmaceuticals. In patients with thyroid cancer, I-131 still plays a significant role. Ga-67 still has its indications in lymphoma, while in other diseases Tl-201 cloride is now the agent of choice. Especially in thyroid cancer, Tl-201 has proved to be a reliable tumor imaging radiopharmaceutical. More recently, Tc-99m MIBI was introduced for tumor imaging. Tc-99m HMPAO may also be used for tumor scintigraphy, especially in brain lesions. In addition, I-123 IMP has successfully been used for imaging malignant melanoma. Another promising field of tumor diagnosis is receptor imaging. In neuroblastoma and malignant pheochromocytoma, I-131/123 mIBG is the radiopharmaceutical of choice and may be considered as a receptor imaging agent also. First clinical results with In-111 octreotide show potentials as somatostatine-receptor radiopharmaceutical in insulinoma, islet cell carcinoma, medullary and lung cancer, while I-123 estradiol needs some improvement until it may be recommended as diagnostic tool in breast cancer. Since 1978, radiolabeled poly- or monoclonal tumor antibodies and their fragments have gained widespread application. Especially the Tc-99m 225.28S melanoma antibody, I-131 or Tc-99m CEA and In-111/I-131 labeled OC-125 antibodies have proven to be of clinical significance in melanoma, colorectal and ovarian cancer.     

Diffuse thoracoabdominal radioactivity seen in bone imaging

Diffusely increased radioactivity in the thoracoabdominal region (lower thorax and/or upper abdomen) occasionally has been observed when performing Tc-99m phosphonate bone studies. To assess the significance of activity in this finding, 1100 bone scintigrams were reviewed and the clinical data and other diagnostic imaging procedures were evaluated in these cases. With the exclusion of Tc-99m sulfur colloid liver-spleen scans 18 patients were found to have mild but diffuse increased radioactivity in the thoracoabdominal region either on the right or left. Clinical findings in these cases with abnormal uptakes were pleural effusions (six cases), hepatic colonic metastases (six cases), splenic metastases from bronchogenic carcinoma (one case), abdominal and peritoneal colonic metastases (one case), a massive metastatic squamous cell carcinoma (from lung) in the right lower chest (one case), and defective radiopharmaceuticals (three cases). Since the defective radiopharmaceuticals contained 5% of hydrolyzed reduced Tc-99m colloid by thin-layer chromatography, each of three patients received approximately 740 mu Ci of Tc-99m sulfur colloid. Factors to be considered in the interpretation of diffuse thoraco-abdominal activity from a bone agent should include splenic or hepatic metastases, a Tc-99m sulfur colloid splenic or hepatic metastases, a Tc-99m sulfur colloid study within the previous 24 hours, pleural effusion, faulty radiopharmaceuticals, and abdominal and peritoneal colonic metastases.     

Anticonvulsants for poisoning by the organophosphorus compound soman: pharmacological mechanisms.

Exposure to high doses of organophosphorus nerve agents such as soman, even with carbamate pretreatment, produces a variety of toxic cholinergic signs, including secretions, convulsions and death. Evidence suggests that soman-induced convulsions may be associated with postexposure brain neuropathology. The purpose of this study was to investigate the pharmacologic mechanism of action of soman-induced convulsions and of anticonvulsant drugs. Various classes of compounds were evaluated for their efficacy in preventing soman-induced convulsions in rats pretreated with the oxime HI-6 to increase survival time, along with various doses of the test compounds (IM) either in the absence or presence of atropine sulfate (16 mg/kg, IM) 30 minutes prior to a soman challenge dose (180 micrograms/kg, SC; equivalent to 1.6 x LD50) that produced 100% convulsions. Without atropine sulfate, only tertiary anticholinergics (scopolamine, trihexyphenidyl, biperiden, benactyzine, benztropine, azaprophen and aprophen), caramiphen, carbetapentane and MK-801 were effective anticonvulsants. In the presence of atropine sulfate, the benzodiazepines (diazepam, midazolam, clonazepam, loprazolam and alprazolam), mecamylamine, flunarizine, diphenylhydantoin, clonidine, CGS 19755 and Organon 6370 studied were effective. We have examined the possibility that diazepam may exert some of its anticonvulsant effects through cholinergic mechanisms and found that a reduced release of ACh into synapses after diazepam and atropine treatment may account for diazepam's anticonvulsant activity against soman. We also found that at anticonvulsant doses biperiden and trihexyphenidyl each significantly reversed the effects of soman on striatal levels of DOPAC and HVA, the metabolites of dopamine, and have concluded that in addition to actions on muscarinic receptors, the anticonvulsant effects of these anticholinergics in soman poisoning may be partially related to their actions on the striatal dopaminergic system. These findings allow us to postulate that central muscarinic cholinergic mechanisms are primarily involved in eliciting the convulsions following exposure to soman and that subsequent recruitment of other excitatory neurotransmitter systems and loss of inhibitory control may be responsible for sustaining the convulsions and for producing the subsequent brain damage. Future studies to confirm these neuropharmacological mechanisms are proposed.     

Cholescintigraphy in the detection of cholelithiasis: a review of 23 cases and a case report demonstrating the sequential evolution of the appearance of the gallbladder defect

Cholescintigraphy of cholelithiasis has been reported as a defect or photon deficient area in the gallbladder. We present the case of a patient with gallstones whose cholescintigraphic study showed a sequential evaluation of the scan appearance from a defect, to a septation, a hole, and finally a filled-in appearance. Cholescintigrams and histopathologic findings after cholecystectomy of another 22 patients with cholelithiasis were also retrospectively reviewed. The results of the study concluded that: cholelithiasis is rarely demonstrated by cholescintigraphy and nonvisualization of the gallbladder may be due to acute or chronic cholecystitis associated with cholelithiasis.     

Calculation of Hydrolytic Rate Constants of Poly(ortho ester)s from Molecular Weights Determined by Gel Permeation Chromatography

Purpose. To obtained rate constants from weight-averaged (M_w) or z-averaged (M_z) molecular weights for polymers of Schule-Flory distribution and undergoing random scission. These constants were compared with those obtained by parallel ¹HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by ¹HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M_n), M_w and M_z into fraction of backbone remaining (f_c) were derived. First-order hydrolytic rate constants of two poly(ortho ester)s; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from ¹HNMR, M_z and M_w were 0.215, 0.218 and 0.182 hr^–1, respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr^–l for DETOSU-HD. The large discrepancy in the rates determined by ¹HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower than that of the high molecular weight polymer. The difference is small in the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from ¹HNMR data. Conclusions. Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.     

Conservative treatment of neonatal hydronephrosis.

From February 1990 to January 1991, 19 cases of hydronephrosis in children of less than one year of age were managed at Mackay Memorial Hospital. In the majority of these patients, there were evident causes such as ureteropelvic junction stenosis, ureterovesical reflux or a posterior urethral valve for which definite therapeutic measures were performed. However, some cases had no obvious origins and the hydronephrosis was speculated to be from nonobstructive or physiologic dilatation of the kidneys. The conventional tools, such as intravenous pyelogram or renal ultrasound, which comprise the mainstay of diagnosis, provide limited information on renal functional status. Recent introduction of the Tc-99m diethylene triamine penta-acetic acid (DTPA) diuretic renal scan has enabled us to distinguish between obstructive and nonobstructive hydronephrosis and helps us to determine whether or not surgery is necessary. In the past year, eight patients with hydronephrosis of less than one year of age were diagnosed as nonobstructive after a series of evaluations using renal ultrasound, voiding cystourethrography (VCUG) and Tc-99m DTPA diuretic renal scan. Follow-up studies by echography or DTPA renal scan revealed spontaneous resolution of the dilated collecting systems in these cases and confirms our belief that some hydronephrosis in neonates and infants may resolve spontaneously and may just be a manifestation of physiologic change during development. The value of the Tc-99m DTPA diuretic renal scan in the diagnosis of obstructive uropathy is discussed.     

Botulism in China

During the period 1958-1983, 986 outbreaks of botulism occurred in China, affecting 4,377 individuals and resulting in 548 deaths. The initial cases of botulism were found in Xinjiang province, where the incidence was highest. Outbreaks have occurred in all of the northern provinces and in some of the southern provinces of China. The toxin found most frequently in the northwest region of China was type A; in north China, type B; and in the northeast, type E. The most frequently offending food was home-made strong-smelling preserved bean curd, which was implicated in 74% of the outbreaks. The complex clinical manifestations of botulism can be grouped into those affecting the eyes, the mouth, the pharynx, and the skeletal muscles. Following the institution of effective methods of prevention and treatment, epidemics of botulism in China have been controlled and the mortality rate reduced from 41% (1950s) to 7.6% (1983).     

Amorphous oxide--a platform for drug delivery.

Usually, a drug is loaded onto the metallic surface of a medical device by applying a polymer layer containing the drug. Unfortunately, polymer coatings on the metallic surface may exhibit numerous problems after implantation, such as late thrombosis, inflammation, and restenosis. Current research was conducted to investigate whether a suitable oxide layer can be used as a polymer-free platform for drug loading, especially for cardiovascular stents. The loading of heparin onto, as well as eluting of heparin from, the amorphous oxide film on the 316LVM stainless steel wire was confirmed by experimental studies using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), electron spectroscopy for chemical analysis (ESCA), high-performance liquid chromatography (HPLC), and activated clotting time (ACT). Evidence shows that amorphous oxide can be an ideal substitute for the polymer coating of drug-loaded stents to minimize metallic corrosion, inflammation, late-thrombosis, and restenosis.