Lymphoscintigraphy of melanoma: lymphatic channel activity guides localization of sentinel lymph nodes, and gamma camera imaging/counting confirms presence of radiotracer in excised nodes.

UNLABELLED: Lymphoscintigraphy has become a standard preoperative procedure to map the cutaneous lymphatic channel for progression of nodal metastasis of melanoma of the skin. Lymphoscintigraphy was employed to visualize lymphatic channels as a guide to identify sentinel lymph nodes (SLNs). Excised tissue was imaged with a gamma camera to verify the findings of presurgical lymphoscintigraphy. Percent counts of SLN(s) among the total counts of the excised melanoma tumor or scar tissue and SLN(s) were calculated. METHODS: Eleven patients with cutaneous melanoma received four to ten intradermal injections of Tc-99m sulfur colloid at elual distances around the melanoma site. Images were made immediately after injection: 1 minute per image for 15 min; and then 5 minutes or 1,000,000 counts per image for 30 min. After surgery, the excised melanoma tumor or scar and SLN(s) were imaged/counted with a gamma camera. Percent counts of SLNs among the total counts of the excised melanoma tumor or scar tissue and SLNs were calculated. To validate the specimen count accuracy, an experimental phantom study was done. RESULTS: Linear lymphatic channels were identified between the injected sites and the SLNs in each patient. Gamma camera images demonstrated radioactivity in the SLNs of all patients, verifying the lymphoscintigraphy findings. Uptake in the SLNs of ten of the eleven patients ranged from 0.4 to 7.2% (mean 2.2%) of the total counts in excised tissue. We noted that a node with lower uptake should not be ignored because a lower percent of SLN activity does not necessarily rule out existing metastasis. In two of eleven patients, histopathologic showed metastases. One patient's melanoma on the middle back had lymphatic channel activity directed to both axillae. The results of the phantom study validated accuracy of our specimen counts. CONCLUSIONS: Because linear lymphatic channels existed between lymph nodes and the injected sites in all eleven patients, these lymphatic channels could be used as a guide for localizing SLNs. The SLNs indicated by presurgical lymphoscintigraphy were verified by postoperative gamma camera imaging, and radiotracer localization in the SLNs averaged 2.2%.

Abnormally increased uptake in the palm and the thumb as the result of a bone imaging agent injection into the radial artery.

The "glove" phenomenon is caused by arterial injection of a bone-imaging agent into the antecubital fossa. The authors describe a patient who incidentally received an arterial injection of bone-imaging agent into the right distal radial artery near the wrist, which resulted in a "hot" palm and thumb. The phenomenon of hot palm and thumb can be explained by normal anatomic-physiologic blood flow after radial artery injection. The radial artery contributes the blood supply to the thumb through the dorsal metacarpal arteries of the first metacarpals, and the dorsal carpal branch of the radial artery, a branch of the interosseous artery, and dorsal carpal branch of the ulnar artery form the dorsal carpal rete. The normal vascular anatomic-physiologic dynamic constituted the mixture and dilution effects after the distal radial artery injection that resulted in hot areas limited to the palm and thumb of the hand on bone scintigraphy.

Evaluation of the feasibility and use of a prototype remote drug delivery capsule (RDDC) for non-invasive regional drug absorption studies in the GI tract of man and beagle dog.

PURPOSE: Evaluate a prototype Remote Drug Delivery Capsule (RDDC) for use in beagle dogs and human volunteers for non-invasive drug absorption studies in different regions of the gastrointestinal tract. METHODS: The device was dual radiolabeled and GI transit of the RDDC was monitored by gamma scintigraphy. Beagles were used initially to demonstrate the functional utility of the device where a solution of ranitidine hydrochloride (150 mg) was non-invasively delivered to the stomach, proximal small intestine and distal small intestine. A subsequent first time in human study enrolled twelve healthy male volunteers where the intended site of release was the stomach, early small bowel, distal small bowel or colon. RESULTS: Preliminary studies conducted in beagles indicated that the RDDC operated successfully and the onset of ranitidine serum levels were dependent on the time of capsule activation and site of drug release. Results from the human study showed that all twelve subjects swallowed the device with no discomfort. Mean gastric emptying of the RDDC was 1.50 +/- 1.28 h (range = 0.25 to 4.25 h), and total small intestine transit was 4.79 +/- 1.82 h (range = 2.00 to 8.25 h). The capsule was retrieved from the feces at 30.25 +/- 15.21 h (range = 14.12 to 74.25 h) and there were no reported adverse events. The prototype RDDC operated successfully in nine of the twelve human volunteers and the cause for the three failures was attributed to mechanical failure while the electronics assembly performed favorably. CONCLUSIONS: This prototype remote control capsule was shown to be well tolerated and functional to use in human volunteers as well as beagles. The application of the device coupled with gamma scintigraphy has the potential to be a valuable and rapid method to non-invasively evaluate regional drug absorption in the gastrointestinal tract under conditions that are both pharmaceutically and physiologically meaningful.

In vivo evaluation of the absorption and gastrointestinal transit of avitriptan in fed and fasted subjects using gamma scintigraphy.

The study was conducted to assess the bioavailability of avitriptan after a standard high fat meal, in relation to gastrointestinal transit. Six healthy male subjects were enrolled in a four-period study with a partial replicate design where each was administered 150-mg avitriptan capsule (i) after an overnight fast, (ii) 5 min after a standard high-fat breakfast, and (iii) 4 hr after a standard high fat breakfast. The treatment administered in Period 3 was repeated in Period 4 to assess intrasubject variations in pharmacokinetics and gastrointestinal (GI) transit. Avitriptan capsules were specially formulated with nonradioactive samarium chloride hexahydrate which was neutron-activated to gamma-emitting samarium before dosing. Serial blood samples were collected for analysis of avitriptan up to 24-hr postdose, and serial scintigraphic images were obtained to assess the plasma concentration-time profile in relation to the GI transit of the avitriptan capsule contents. Bioavailability of avitriptan was reduced when administered in the fed condition but only the decrease in AUC(INF) was statistically significant. Tmax was significantly delayed between the fed conditions and the fasted condition. Qualitative appearance of plasma concentration-time profiles for avitriptan could be related to the manner in which the drug emptied from the stomach. It was also apparent that avitriptan exerted a secondary pharmacologic effect that temporarily suspended gastric emptying in the fasted treatment. Thus, when gastric emptying was interrupted and then resumed, the net result was a double peak in some of the individual plasma concentration profiles. Scintigraphic analysis also demonstrated that upon emptying from the stomach, avitriptan was rapidly absorbed from the upper small intestine. In the fed state, gastric emptying was slow and continuous resulting in extended absorption and a lower occurrence of double peaks. Qualitatively, the intrasubject variability in Cmax and AUC could be explained by the intrasubject variability in gastric emptying in both fasted and fed conditions.

A normal technetium-99m-DTPA renogram in renal cell carcinoma: a case report.

A 64-yr-old man with a renal mass had a preoperative 99mTc-DTPA renal flow study and renogram. An area of minimally relative increase in flow in the upper half of the right kidney was thought to reflect the high vascularity of the renal mass. A subsequent renogram showed no mass defect in the area of relatively high flow of the right kidney. The patient had a right nephrectomy. The removed kidney showed an extrarenal mass measuring 6 x 5.5 x 5 cm at the upper pole of the kidney. The mass was confirmed to be a renal cell carcinoma, clear cell type. There was no renal tissue invasion. These finding suggest an extrarenal mass pattern may be difficult to identify with a normal appearing renogram.

Explaining variable absorption of a hypolipidemic agent (CGP 43371) in healthy subjects by gamma scintigraphy and pharmacokinetics.

The gastrointestinal absorption of a hypolipidemic agent (CGP 43371) was investigated using an external scintigraphy technique in six healthy men. After an overnight fast, subjects received a single 800-mg oral dose of CGP 43371 (4 capsules of 200 mg each) and one capsule of radioactive samarium-153 oxide (100-130 microCi) as a nonabsorbable marker of gastrointestinal transit and fecal recovery for CGP 43371. In vivo gastrointestinal transit of samarium-153 was monitored via gamma scintigraphy for 48 hours after administration to coincide with blood sampling. Samarium-153 content in whole fecal samples was determined by external gamma scintigraphy, and CGP 43371 content in both fecal and plasma samples was determined using high-performance liquid chromatography (HPLC). The results of fecal analysis indicated that transit of the two compounds in the gastrointestinal tract were similar, and bioavailability of CGP 43371 was calculated to be 9% based on the difference between the cumulative amounts of the nonabsorbable radioactive marker and CGP 43371 found in the feces. The onset of drug absorption occurred 4 hours after administration when radioactive samarium-153 was in the distal small bowel, and peak plasma drug level occurred 6 hours after administration, which corresponded with the arrival of samarium-153 in the terminal ileum and ileal/cecal junction. This observation supported the concept that primary absorption of this compound was in the distal to terminal portion of the ileum. Although the onset of drug absorption was delayed, it was curious that the rate of gastric emptying also affected the extent of absorption. A positive correlation (r = 0.91) between area under the drug curve (AUC) and area under the transit curve (AUTC) of the gastric emptying showed that longer gastric residence improved oral absorption of CGP 43371.

Morphine-augmented cholescintigraphy enhances duodenogastric reflux.

Morphine intervention in cholescintigraphy decreases imaging time to diagnose acute cholecystitis. Not infrequently we observe duodenogastric reflux during scintigraphy with and without morphine intervention. To evaluate occurrence of duodenogastric reflux related to morphine, we reviewed 55 patients who underwent cholescintigraphy with (32) and without (23) morphine intervention. Morphine was injected when there was bowel activity with non-visualization of the gallbladder at 60 min. Duodenogastric reflux was identified by the appearance of activity in the area just below or immediately adjacent to the tip of the left hepatic lobe laterally. Among 32 patients with morphine intervention, 19 had acute cholecystitis and 13 chronic cholecystitis. Eleven of 19 (58%) with acute cholecystitis had duodenogastric reflux and 6 of 13 (46%) had duodenogastric reflux in chronic cholecystitis. The total of duodenogastric reflux in the group with morphine injection was 53%. Two patients' duodenogastric reflux occurred before morphine injection and was more apparent after morphine was given. In the without morphine group, 3 had acute cholecystitis and 20 had chronic cholecystitis; 2 (one acute and one chronic cholecystitis) of these 23 (9%) had duodenogastric reflux. Our results indicate: (1) occurrence of DG reflux in morphine augmented cholescintigraphy is not significantly different in cholecystitis from that in chronic cholecystitis; (2) duodenogastric reflux in morphine augmentation occurs significantly more often than without morphine intervention (p < 0.001). We conclude that cholescintigraphy with morphine enhances duodenogastric reflux. The degree of duodenogastric reflux in the acute cholecystitis patients has been more severe than in the chronic cholecystitis patients.

Images of estrogen-receptor-positive breast tumors produced by estradiol labeled with iodine I 123 at 16 alpha.

OBJECTIVE: To examine the suitability of estradiol labeled with iodine I 123 at 16 alpha for imaging estrogen-receptor-positive breast carcinoma using imaging instrumentation that is widely available. DESIGN: Single-photon emission computed tomographic imaging survey of 29 women with suspected primary or expected recurrent breast carcinoma. SETTING: University-based referral center. PARTICIPANTS: Twenty-nine women undergoing diagnosis for primary or recurrent breast carcinoma. Selection was voluntary. MAIN OUTCOME MEASURE: Qualitative imaging study designed to provide tomographic data of radioligand retention and descriptive data of imaging results. RESULTS: Single-photon emission computed tomographic imaging using 123I-estradiol at 16 alpha was performed for patients with breast carcinoma. Independent readers, without knowledge of receptor status or proven disease, interpreted the films. Scintigraphic detection was most noteworthy in patients with chest wall tumors and inflammatory breast cancer. Agreement between readers was 98% for true-negative readings and 94% for true-positive readings, but only 60% for false-positive and false-negative film readings. CONCLUSIONS: Our results indicated that areas shown on imaging were also found to have estrogen-receptor activity and that radioligand accumulation can occur with low frequency in some surgically explored tissue. Radioligand imaging with 16 alpha-123I-estradiol can locate estrogen-receptor-positive breast tumors, including some that may be difficult to detect using conventional diagnostic imaging.

Tc-99m sestamibi uptake by cerebellar metastasis from bronchogenic carcinoma.

Tc-99m sestamibi has been used to detect primary brain and lung tumors. The authors report a patient who underwent brain imaging to differentiate tumor from abscess in the cerebellum because of a ring-like enhancement lesion on a brain CT scan. An abnormal area of increased sestamibi uptake in the right cerebellum was demonstrated planar and on a SPECT imaging. The removed tumor was confirmed to be poorly differentiated metastatic carcinoma.

Lung uptake of Tc-99m HMPAO in cigarette smokers expressed by lung/liver activity ratio.

Tc-99m HMPAO, a lipophilic radiopharmaceutical used for brain imaging, has been reported to localize in smokers' lungs. To quantitate this uptake in the lung, 55 patients, who were referred for brain imaging for dementias or strokes, also underwent lung imaging (anterior lung imaging includes a large part of the liver) after IV injection of the radiopharmaceutical. Regions of interest over the liver and the lung were calculated. Of the 55 patients (ages 13-79), 30 were smokers and 25 were nonsmokers. The smokers had been smoking from 6-59 years, and daily cigarette consumption ranged from 8-50 cigarettes. The mean lung/liver ratio for smoking patients were 0.792 +/- 0.042 (SE); the mean lung/liver ratio for nonsmoking patients was 0.408 +/- 0.019 (SE). Lung/liver ratio uptake was significantly higher in the smoking patients (P < 0.01) than in the nonsmokers. Thus, lung/liver uptake of Tc-99m HMPAO may be used as an indicator of cigarette smoking.

Prostate adenocarcinoma using Gleason scores correlates with prostate-specific antigen and prostate acid phosphatase measurements.

To evaluate a relationship between Gleason scores of histopathology of prostate carcinoma and concurrent serum prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) values, 65 men with prostate carcinoma were studied. These patients' cumulative Gleason scores were obtained by totaling the primary and secondary patterns, resulting in two groups: 42 patients received high (6-10) and 23 received low (2-5) Gleason scores. Serum PSA and PAP values were measured by radioimmunometric assay 1 to 7 days before surgical procedures or biopsy for prostate carcinoma. Mean serum PSA for patients in the high Gleason score group was 134.39 ng/mL (normal range: 0 to 4), and the mean serum PSA for patients in the low Gleason score group was 23.62 ng/mL. Mean serum PAP for patients with high scores was 28.08 ng/mL (normal range: 0 to 5), and the mean serum PAP for patients with low scores was 18.19 ng/mL. Patients with high Gleason scores showed significantly greater elevation of serum PSA than those with low Gleason scores (P = .047), using two samples to test for groups having unequal variants. Prostate acid phosphatase levels of patients with high scores were not significantly higher than the levels in patients with low scores (P = .60). These results indicate that PSA levels but not PAP levels correlate with Gleason scores.

Noninvasive detection of Helicobacter pylori colonization in stomach using [11C]urea.

Helicobacter pylori is associated with chronic type B gastritis. Diagnosis can be made on gastric biopsy specimens and noninvasively using [13C]- or [14C]urea breath tests. Both breath tests require meticulous breath collection, and false positive results are possible from urease producing oral-pharyngeal flora. We used [11C]urea, a positron-emitting radionuclide allowing dynamic imaging, to measure metabolism of urea in the stomach of biopsy documented H. pylori-positive patients. [11C]urea was synthesized from 11CO2 produced using a Van de Graaff accelerator and administered with [99mTc]DTPA to control for loss of radioactivity via gastric emptying. Images were obtained externally by gamma camera every minute and 11CO2 was monitored in the breath continuously for 30 min. An H. pylori-positive patient exhibited a 99mTc/11C activity ratio of 2:1 in the stomach 10-20 min following administration, compared to a 1:1 ratio in a negative control, indicating metabolism of urea to 11CO2 with subsequent diffusion of 11C activity out of the stomach. The 11C activity in the breath peaked at 10-20 min in the H. pylori-positive patients. The short half-life of carbon-11 (20.4 min) alleviates radiation safety concerns and results in low absorbed radiation doses to patients.

Polymeric microspheres for radionuclide synovectomy containing neutron-activated holmium-166.

Poly-L-lactic acid (PLA) microspheres containing neutron-activated 166Ho were investigated as potential agents for radionuclide synovectomy. Stable 165Ho, complexed to acetylacetone (AcAc), was incorporated into PLA spheres by the solvent evaporation technique. Spheres prepared with the optimal mean particle size of 7.2 microns (range 2-13 microns) containing 25.4% 165Ho-AcAc (9.1% 165Ho) were irradiated in a high neutron flux to produce 31.1-36.0 mCi 166Ho. In vitro human plasma studies showed that the irradiated spheres retained 99.0 +/- 0.01% of the 166Ho at 314 hr. In-vivo retention studies were conducted by administering irradiated PLA spheres with 257-591 microCi 166Ho into the joint space of normal rabbits (n = 6). Biodistribution analysis and gamma camera analysis showed 166Ho retention in the joint space after 120 hr of 97.7% +/- 0.8% and 98.2% +/- 2.4%, respectively, with no uptake by the lymph nodes. The ease with which the PLA spheres can be made in the optimal size range for later irradiation and their ability to retain the 166Ho make them attractive agents for radionuclide synovectomy.

Neutron-activated holmium-166-poly (L-lactic acid) microspheres: a potential agent for the internal radiation therapy of hepatic tumors.

Biodegradable Poly(L-lactic acid) microspheres containing neutron-activable 165Ho were designed for internal radiation therapy of hepatic tumors. Spheres composed of Poly(L-lactic acid) (PLA) were prepared with excellent reproducibility containing up to 36% of a holmium complex. The prepared spheres were irradiated in a high neutron flux converting 165Ho to 166Ho (Emax = 1.84 MeV, half-life = 26.9 hr). Thus, these microspheres can be prepared under conditions that do not require the handling of a hazardous radionuclide, and then irradiated just prior to administration. In vitro studies in plasma (n = 6) revealed 97.3% (+/- 1.9) retention of 166Ho in the microspheres after 240 hr. PLA spheres administered via the portal vein in rabbits (n = 6) show 94.5% (+/- 3.4) retention of the original 166Ho activity in the liver after 6 days.

Prediction of radionuclide bone imaging findings by Gleason histologic grading of prostate carcinoma.

To evaluate a relationship between Gleason scores and Tc-99m HMDP bone imaging findings, data from 48 men (aged 45 to 77; mean, 67) with prostate carcinoma who had a bone imaging study at the time of presentation were reviewed. Cumulative Gleason scores were divided into two groups: high scores (6-10), 32 men; low scores (2-5), 16 men. Of the 32 men with high Gleason scores, 15 tested positive for multiple metastases and 17 tested negative. Tumors of the 16 men with low Gleason scores were negative for metastasis. A chi-square association between Gleason scores and the presence of metastases, either of a superscan pattern or multiple metastases, was 10.9 (1 df, P less than 0.001). The results indicate that a superscan pattern or multiple metastases were found exclusively in the bone images of patients with high histologic grades; bone images negative for metastases were associated with low-grade tumors. We conclude that positive bone imaging for metastases at the initial scan occurs only in patients who have high Gleason scores, that patients with high Gleason scores might or might not have skeletal metastasis, and that skeletal metastasis is not predictable in patients with low Gleason scores.