Melvin J. Fratkin

A pharmacokinetic evaluation of 14C-labeled afovirsen sodium in patients with genital warts.

Afovirsen sodium is a 20‐mer phosphorothioate oligonucleotide designed to be complementary to the messenger ribonucleic acid sequence for the translation initiation codon of the E2 protein vital to replication of human papillomaviruses types 6 and 11. 14C‐Labeled afovirsen was given as a single‐dose intradermal injection in each of four warts of five patients to determine the time‐dependent changes in concentration of intact afovirsen in genital warts and to determine the systemic absorption and elimination of radiolabeled compound. Intact afovirsen in genital warts was determined by high pressure liquid chromatography analysis of protease K digested extracts. Intact afovirsen was present in wart tissue for at least 72 hours at concentrations several times in excess of the estimated minimal inhibitory concentration of 1 µmol/L. Absorption of radiolabeled afovirsen from the injection site was rapid, with a peak plasma concentration achieved within 1 hour. Clearance of afovirsen was primarily attributable to slow metabolism, with about 30% of the radiolabel eliminated as 14C‐CO2 in expired air over a 6‐day period after dosing. Radioactivity eliminated in urine represented metabolites of afovirsen. From the clinical pharmacokinetic data presented here and from previously published pharmacokinetic data in rats, the disposition of afovirsen in humans appears to be relatively similar to that in rats. These data suggest that once or twice weekly dosing regimen in the clinic may be appropriate.

Arthroscintigraphic evaluation of the painful total hip prosthesis.

Arthroscintigraphy was performed in 19 patients with a painful total hip prosthesis by injecting both Tc-99m sulfur colloid and iodinated radiographic contrast material intra-articularly. Scintigraphic and radiographic results correlated exactly in 15 patients, with one false-negative scintigram, one false-positive scintigram, and one false-negative arthrogram. One patient was evaluated by scintigraphy alone. Although arthroscintigraphy is potentially more sensitive than conventional arthrography in the detection of femoral component loosening, acetabular component loosening cannot be evaluated by scintigraphy alone. A combination of scintigraphy and conventional arthrography appears to be the most accurate imaging method in the evaluation of hip prosthesis loosening.

Pitfall to modified in vivo method of technetium-/sub 99m/ red blood cell labeling. Iodinated contrast media

Suboptimal labeling of red blood cells with Tc–99m, using the modified in vivo technique, was observed in three patients in whom labeling was attempted following IV administration of iodinated contrast media in the previous 24 hours. The mechanism is not understood, but it may represent a change in either stannous ion distribution or redox potential. It is recommended that studies employing Tc–99m RBC labeling using this technique be performed prior to administration of iodinated contrast media. This effect should be kept in mind in gastrointestinal bleeding studies performed using Tc–99m RBC, as well as in cardiac imaging studies.

Gallium Scanning and Inflammatory Lesions

Excerpt To the editor: Although originally intended for use as a bone-scanning agent,67Ga was seen to localize in soft tissue tumors (1). Littenberg and colleagues (Ann Intern Med79:403-406, 1973) ...

Accumulation of Tc-99m MDP in amyloidosis involving the tongue.

Radionuclide bone imaging using Tc-99m phosphates may show accumulation of activity in amyloid deposits. While many sites of amyloidosis have been detected with bone imaging, many reports center on cardiac amyloidosis. The case reported here demonstrates accumulation of Tc-99m MDP in amyloidosis involving the skin and muscle, including the tongue.

Determinants of diagnostic accuracy in pulmonary scintigraphy for pulmonary capillary protein leak associated with adult respiratory distress syndrome (ARDS): A technical note

Radionuclide assessment of pulmonary capillary protein leak using [99mTc] human serum albumin (99mTc-HSA) was first reported from our laboratory. In this study we investigated the impact of 1) sampling time post tracer injection, and 2) lung region assignment, on diagnostic accuracy between 2 groups (controln=20 and ARDSn=20). Each patient received 370 MBq99mTc-HSA i.v. and was imaged for 45 min. The slope index (SI) [change in lung: heart activity ratio/min] was calculated from 11 computer assigned lung regions for intervals of 5–15 (early [E]) and 15–45 (late [L]) min. The diagnostic accuracy of E vs L SI calculations for the 11 regions was evaluated by stepwise logistic regression. E SI data and L SI data from the lower 1/3 of the lung did not achieve significance for inclusion in the discriminant model (P<0.05). In the nine remaining regions L SI was significant. Optimal discrimination was achieved from L SI data obtained from a region confined to the lateral half of the mid 3rd of the lung field (sensitivity 81%, specificity 85%, accuracy 83%). The results confirm that: 1) a late (15–45 min) sampling period and 2) proper region assignment are necessary to maximize accuracy of this technique.

Artifactual focal accumulation of Tc-99m bone imaging tracer in the chest. Technical note (bone imaging artifact).

Four patients undergoing routine bone imaging with a Tc-99m bone imaging agent were observed to have multiple focal areas of increased uptake in the lungs. Delayed or repeat examination demonstrated resolution of the areas. The authors conclude that this was an isolated and bizarre case of aggregate formation.

Significance of alteration in biodistribution of labeled lymphocytes exposed to stannous ion

The biodistribution patterns of 99mTc (99mTc-lymph) and 111In-lymphocytes with [111In-(Sn)-lymph] or without (111In-lymph) stannous ion treatment was compared in Lewis rats. Syngeneic lymphocytes were labeled with either 125 μCi (4.63 MBq) 99mTc or 5 uCi (1985 kBq) 111In per 2×107 cells. Mean labeling efficiency for 99mTc and 111In was 68.61%±3.90% (SEM) and 87.22%±2.01% (SEM) respectively. 99mTc-lymph (n=4), 111In-lymph (n=6) and 111In-(Sn)-lymph (n=6) rats received 2x107 cells and were killed 18 h later. While 99mTc-lymph demonstrated significantly less localization in spleen, lymph nodes, and blood (P(F)0.01) as compared with 111In-lymph, 111In-(Sn)lymph also demonstrated a significant difference (P[F]=0.0001) in lymph node accumulation when compared to 111In-lymph. As the activity levels utilized are not associated with cell radiation damage, these alterations in biodistribution do not reflect viability or chromosomal damage, but appear related to stannous ion exposure.

Relative decreased splenic uptake of Tc-99m-sulfur colloid in patients with pancreatic carcinoma

Relative spleen/liver activity ratio was determined from posterior projection images using a photodensitometric method. Ratios from scans of 22 patients with proven pancreatic carcinoma (12 from rectilinear scans and 10 from scintillation camera images) were determined and compared to studies from patients documented as normal and to randomly selected liver/spleen imaging studies which had been previously interpreted as normal. The mean ratio from the pancreatic carcinoma group was significantly lower than the means of the respective normal groups (p[t] < .0001 for rectilinear scans and p[t] < .001 for scintigrams). There was no significant difference between the means of the proven normal and randomly selected normal groups or between the two pancreatic carcinoma groups. Splenic vascular alteration is discussed as a possible reason for decreased splenic distribution of Tc-99m-sulfur colloid in this patient group.

Localization of the renal cortical imaging agent 99mTc-Sn-DMSA in the bowel.

Renal imaging in 2 patients with severe renal disease (serum creatinine greater than 10 mg/dl) showed deposition of 99mTc-Sn-DMSA in the bowel. Like 203 Hg-chlormerodrin, this radionuclide may be associated with a hepatobiliary excretory mechanism in patients with renal impairment.