Contralateral adrenal suppression on adrenocortical scintigraphy provides good evidence showing subclinical cortisol overproduction from unilateral adenomas.

Unilateral and/or predominant uptake on adrenocortical scintigraphy (ACS) may be related to autonomous cortisol overproduction in patients with subclinical Cushing's syndrome (SCS). However, there is no information regarding whether increased tracer uptake on the tumor side or decreased uptake on the contralateral side on ACS is more greatly associated with inappropriate cortisol production. Therefore, we evaluated the relationship between quantitative 131I-6ß-iodomethyl-norcholesterol (131I-NP-59) uptake in both adrenal glands and parameters of autonomic cortisol secretion and attempted to set a cut off for SCS detection. The study included 90 patients with unilateral adrenal adenoma who fulfilled strict criteria. The diagnosis of SCS was based on serum cortisol ≥3.0 µg/dL after 1-mg dexamethasone suppression test (DST) with at least 1 other hypothalamus-pituitary-adrenal axis function abnormality. Twenty-two (27.7%) subjects were diagnosed with SCS. The uptake rate on the affected side in the SCS group was comparable to that in the non-functioning adenoma group. In contrast, the uptake rate on the contralateral side was lower and the laterality ratio significantly higher in the SCS group. The two ACS indices were correlated with serum cortisol levels after a 1-mg DST, but uptake on the tumor side was not. Tumor size was also important for the functional statuses of adrenal tumors and NP-59 imaging patterns. The best cut-off point for the laterality ratio to detect SCS was 3.07. These results clearly indicate that contralateral adrenal suppression in ACS is good evidence showing subclinical cortisol overproduction.

Functional imaging of adrenal cortex. / Estudios de imagen funcional de la corteza adrenal.

The rising number of high-resolution imaging scans has increased the adrenal lesions detection, which require a differential diagnosis. Currently, the most commonly used scans are CT and MRI, but these are sometimes not very specific. In these cases, nuclear medicine scans with 131I-norcolesterol, 11C-metomidate and 18F-fludeoxyglucose help to differentiate benign vs. malignant lesions, to lateralize the involvement in hypersecretion disease, as well as to guide the therapeutic strategy in both unilateral and bilateral lesions.

The value of 18F-FDG PET-CT and 131I-norcholesterol scintigraphy in the characterization of high-risk adrenal masses.

PURPOSE: To assess the value of F-FDG PET-computed tomography (CT) and I-norcholesterol scintigraphy in noninvasive characterization of high-risk adrenal lesions using surgical pathology as the gold standard. METHODS: We retrospectively reviewed clinical cases referred to the adrenal multidisciplinary team in a tertiary centre over the last 6 years. Inclusion criteria were the presence of indeterminate adrenal lesions and performance of combined imaging with 2-deoxy-2-[fluorine-18] fluoro- D-glucose Positron emission tomography/ computed tomography and I-norcholesterol scans. The accuracy of CT, PET-CT and I-norcholesterol findings was assessed by comparison with the postoperative histopathological outcome. RESULTS: Sixteen patients fulfilled the inclusion criteria. Ten underwent unilateral adrenalectomy, and six had clinical follow-up. The number of cases categorized as concerning on the basis of unenhanced CT, F-FDG PET-CT and I-norcholesterol was 11, 9 and 2, respectively. The mean diameter of adrenal lesions was 4.5 ± 1.9 cm. Average SUVmax of the FDG-avid adrenal lesions was 5.0 ± 2.0 (range 3.5-9.7). Fourteen adrenal masses showed I-norcholesterol uptake. All adrenal masses turned out to be benign lesions. CONCLUSION: Conventional CT and FDG PET parameters are not adequately specific for determination of a benign lesion in this selected cohort of high-risk patients. Use of I-norcholesterol in this patient cohort may provide additional value.

131I-6ß-iodomethyl-19-norcholesterol adrenal scintigraphy as an alternative to adrenal venous sampling in differentiating aldosterone-producing adenoma from bilateral idiopathic hyperaldosteronism.

OBJECTIVE: To assess the correlation value between adrenal venous sampling (AVS) and I-6ß-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy in differentiating aldosterone-producing adenoma (APA) from bilateral idiopathic hyperaldosteronism (BHA), and the use of NP-59 scintigraphy as an alternative to AVS. METHODS: Overall, 29 patients with APA or BHA who underwent AVS and dexamethasone-suppression NP-59 scintigraphy were included between 2010 and 2017. The correlation value between AVS and dexamethasone-suppression NP-59 scintigraphy was assessed using each lateralisation index (LIAVS and LI1NP-59). Tumour presence and size were evaluated using computed tomography. The sensitivity and specificity of dexamethasone-suppression NP-59 scintigraphy for APA according to each lateralisation index threshold were calculated. RESULTS: Of 29 patients, 12 presented with APA and 17 with BHA according to AVS. The correlation value between LIAVS and LI1NP-59 was 0.63 (P < 0.001). If the cut-off points were 2.55 and 1.80 in all cases, the sensitivity and specificity were 0.33 and 1.00 as well as 0.58 and 0.94, respectively. In adrenal microtumours (maximum diameter ≤10 mm), no cases revealed a cut-off point of >1.8. However, in adrenal macrotumours (maximum diameter >10 mm), the cut-off point of 2.55 represented the best compromise (sensitivity: 0.44; specificity: 1.00). CONCLUSION: NP-59 scintigraphy can be used as an alternative to AVS if there is a strong lateralisation on NP-59 scintigraphy and adrenal macrotumours observed on the computed tomography when AVS is technically challenging, particularly in the right adrenal vein cannulation, and if contraindications, such as allergy to contrast materials and renal failure, are observed.

Diagnostic value of adrenal iodine-131 6-beta-iodomethyl-19-norcholesterol scintigraphy for primary aldosteronism: a retrospective study at a medical center in North Taiwan.

BACKGROUND: Primary aldosteronism (PA) is a common cause of secondary hypertension. Among the many leading causes of PA, the two most frequent are, bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenomas (APA). Since a solitary APA may be cured surgically, but BAH needs lifelong pharmacologic therapy, confirmation is mandatory before surgery. We herein sought to determine the diagnostic value of iodine-131 6-beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy to distinguish BAH from APA. PATIENTS AND METHODS: Patients clinically suspected of PA from March 2000 to October 2016 were retrospectively analyzed. A total of 145 patients, including 74 postunilateral adrenalectomy and seven postradiofrequency ablation for adrenal mass, were reviewed. All patients received NP-59 adrenal scintigraphy prior to surgery. The accuracy of the NP-59 adrenal scintigraphy was confirmed by the pathologic findings and postoperative outcomes. RESULTS: Among 81 patients receiving interventional procedures for adrenal mass, adenoma was eventually diagnosed in 72 patients according to their pathologic results, with 60 unilaterally and seven bilaterally localized lesions by NP-59 scintigraphy; nevertheless, there were five negative findings initially. The sensitivity, specificity, and positive predictive value of NP-59 scintigraphy for APA detection were therefore 83.3, 44.4, and 92.3%, respectively. Moreover, single-photon emission computed tomography/computed tomography scan increased the sensitivity and specificity, but not the positive predictive value (85.0, 60.0, and 89.5%) of NP-59 scintigraphy in this study. CONCLUSION: NP-59 adrenal scintigraphy is a useful imaging test to detect APA. Lateralization by this modality prior to surgical intervention may reduce the need for such invasive procedures as adrenal venous sampling.

Biocompatibility evaluation of crosslinked chitosan hydrogels after subcutaneous and intraperitoneal implantation in the rat.

The aim of the present study was to evaluate the toxicity of biodegradable hydrogels in the rat with a future aim of utilizing this hydrogel as a vehicle for brachytherapy delivery in cancer patients. Two types of chitosan hydrogels: fast degrading and slow degrading; were prepared and surgically implanted in rats. The adjacent tissue response to the gels after subcutaneous and intraperitoneal implantation was examined histologically and found to be identical to typical foreign body response and was milder than the response to absorbable surgical sutures (Vicril). Neither tissue damage nor gel fragments could be detected in distant organs (brain, heart, lungs, liver, spleen, kidney, and sternal bone marrow) after implantation of the hydrogels. The degradation mechanism of the gels was studied in vivo, and it was deduced that an oxidative process degraded the chitosan. Loading the hydrogels with a radioisotope (131I-norcholesterol) caused a severe tissue response and necrosis in adjacent tissues only at a distance of several microns. It is concluded that crosslinked chitosan implants could serve as alternative, biocompatible, and safe biodegradable devices for radioisotope delivery in brachytherapy for cancer.

High risk of malignancy in patients with incidentally discovered adrenal masses: accuracy of adrenal imaging and image-guided fine-needle aspiration cytology.

AIMS AND BACKGROUND: The incidental finding of nonfunctioning adrenal masses (incidentalomas) is common, but no reliable criteria in differentiating between benign and malignant adrenal masses have been defined. The aim of this preliminary study was to assess the usefulness of adrenal imaging and image-guided fine-needle aspiration cytology in patients with nonfunctioning adrenal incidentalomas with the aim of excluding or confirming malignancy before surgery. METHODS: Forty-two consecutive patients (18 men and 24 women; median age, 54 years; range, 25-75 years) with incidentally discovered adrenal masses of 3 cm or more in the greatest diameter were prospectively enrolled in the study. All patients underwent helical computerized tomography scan and image-guided fine-needle aspiration cytology, 33 (78.6%) underwent magnetic resonance imaging, and 26 (61.9%) underwent norcholesterol scintigraphy before adrenalectomy. RESULTS: The revised final pathology showed 30 (71.4%) benign (26 adrenocortical adenomas, of which 3 were atypical, 2 ganglioneuromas, and 2 nonfunctioning benign pheochromocytomas) and 12 (28.6%, 95% CI = 15-42) adrenal malignancies (8 adrenocortical carcinomas and 4 unsuspected adrenal metastases). The definitive diagnosis of adrenocortical carcinoma was made according to Weiss criteria and confirmed on the basis of local invasion at surgery or metastases. The sensitivity, specificity and accuracy were 75%, 67% and 83% for computerized tomography scan, 92%, 95% and 94% for magnetic resonance imaging, 89%, 94% and 92% for norcholesterol scintigraphy, and 92%, 100% and 98% for fine-needle aspiration cytology. The sensitivity and accuracy of image-guided fine-needle aspiration cytology and magnetic resonance imaging together reached 100%. Immediate periprocedural complications of fine-needle aspiration cytology occurred in 2 (4.7%) patients: self-limited pneumothorax (n = 1), and severe pain (n = 1) requiring analgesic therapy. No postprocedural or late complications were observed. CONCLUSIONS: With the aim of selecting for surgery patients with a non-functioning adrenal incidentaloma of 3 cm or more in diameter, the combination of magnetic resonance imaging and fine-needle aspiration cytology should be considered the strategy of choice.

Crosslinked chitosan implants as potential degradable devices for brachytherapy: in vitro and in vivo analysis.

Compared with conventional external beam radiation, brachytherapy offers a superior therapeutic regimen. However, some major constraints are associated with its implementation, including the need of complicated procedures for device placement and removal. The purpose of this study was to examine whether crosslinked chitosan (Ct) implants could serve as potential biodegradable devices for brachytherapy. Ct was reacted with increasing amounts of glutaraldehyde to obtain hydrogels with different crosslinking densities, which were characterized chemically, thermally and mechanically. The effect of the dialysis medium conditions (ionic strength, osmolarity and pH) on the gel hydration and in vivo degradation was assessed. Two types of implants, slow and fast degrading gel (SDG and FDG, respectively), were prepared and implanted with or without Sudan Black (SB) in the rat. While SDG withstood for over a month, the FDG degraded within two weeks after implantation. The release kinetics of SB from the hydrogels verified their in vivo degradation properties. The incorporation of the radioactive compound (131)I-norcholesterol ((131)I-NC) into the SDG altered the degradation kinetics of the gel as reflected by the release kinetics of the radioactive marker. Eighty percent of (131)I-NC was released within a month after implantation, after which time, radioactivity was detected in the regional lymph nodes. Histological examination of the tissues surrounding the implants demonstrated negligible tissue response to the implants, when compared to biodegradable surgical sutures. It is concluded that hydrogels made of crosslinked Ct are potential novel, safe, degradable devices for brachytherapy.

A case of ganglioneuroma in which 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol scintigraphy showed high uptake in the adrenal gland leading to a misdiagnosis.

We experienced a case in which 131I-6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol (131I-adosterol) scintigraphy showed high uptake in the right adrenal gland. We diagnosed functional cortical adenoma because of the finding of 131I-adosterol scintigraphy. However, no positive findings for the existence of cortical adenoma were obtained in other examinations and we performed right adrenalectomy. Unexpectedly, pathological finding showed the right adrenal gland was occupied with a large ganglioneuroma. This is an instructive case in which 131I-adosterol scintigraphy showed abnormal high uptake in the adrenal gland, in spite of the fact that the adrenal gland was occupied by a tumor derived from adrenal medulla.

Value of bowel preparation in adrenocortical scintigraphy with NP-59.

The use of radiolabeled cholesterol derivatives for functional imaging of the adrenal cortex may be rendered inaccurate or impossible because of the excretion of activity by the liver and its subsequent appearance in the colon. A simple bowel preparation (bisacodyl 5 or 10 mg nightly) significantly reduced bowel background activity during 6 beta-[I-131]iodomethyl-19-norcholesterol (NP-59) adrenal cortical scintigraphy. Activity interfering with image interpretability was present less frequently in patients taking bisacodyl: three days after injection 22% compared with 59%; five days after injection 23% compared with 35%. As bisacodyl acts only on the colon and does not disturb the enterohepatic circulation of cholesterol or bile acids, it is ideal for use with a tracer of cholesterol metabolism.

The diagnostic role of radionuclide imaging in evaluation of patients with nonhypersecreting adrenal masses.

UNLABELLED: The aim of this study was to evaluate the role of radionuclide imaging in the characterization of nonhypersecreting adrenal masses. METHODS: A total of 54 patients (19 men, 35 women; mean age, 50 +/- 16 y) with nonhypersecreting unilateral adrenal tumors that had been originally detected on CT or MRI underwent adrenal scintigraphy using different radiotracers. None of the patients showed specific symptoms of adrenal hypersecretion. Screening tests for excess cortical and medullary products showed normal adrenal hormone levels. Radionuclide studies (n = 73) included (131)I-norcholesterol (n = 24), (131)I-metaiodobenzylguanidine (MIBG) (n = 23), and (18)F-FDG PET (n = 26) scans. RESULTS: Histology after surgery (n = 31) or adrenal biopsy (n = 23) was obtained. Adrenal lesions were represented by 19 adenomas, 4 cysts, 1 myelolipoma, 1 neurinoma, 2 ganglioneuromas, 5 pheochromocytomas, 4 pseudotumors, 6 carcinomas, 2 sarcomas, and 10 metastases (size range, 1.5- to 5-cm diameter; mean, 4.9 +/- 3.1 cm). For norcholesterol imaging, diagnostic sensitivity, specificity, and accuracy were 100%, 71%, and 92%, respectively; the positive predictive value (PPV) of the norcholesterol scan to characterize an adrenal mass as an adenoma was 89%, whereas the corresponding negative predictive value (NPV) to rule out this type of tumor was 100%. For MIBG imaging, diagnostic sensitivity, specificity, and accuracy were 100%, 94%, and 96%, respectively; the PPV of the MIBG scan to characterize an adrenal mass as a medullary chromaffin tissue tumor was 83%, whereas the corresponding NPV to rule out this type of tumor was 100%. For FDG PET, diagnostic sensitivity, specificity, and accuracy were 100%, 100%, and 100%, respectively; the PPV of FDG PET to characterize an adrenal mass as a malignant tumor was 100%, whereas the corresponding NPV to rule it out was 100%. Furthermore, in 7 patients with malignant adrenal tumors, FDG whole-body scanning revealed extra-adrenal tumor sites (n = 29), allowing an accurate diagnosis of the disease's stage using a single-imaging technique. CONCLUSION: In patients with nonhypersecreting adrenal masses, radionuclide adrenal imaging, using specific radiopharmaceuticals such as norcholesterol, MIBG, and FDG, may provide significant functional information for tissue characterization. Norcholesterol and MIBG scans are able to detect benign tumors such as adenoma and pheochromocytoma, respectively. Conversely, FDG PET allows for recognition of malignant adrenal lesions. Therefore, adrenal scintigraphy is recommended for tumor diagnosis and, hence, for appropriate treatment planning, particularly when CT or MRI findings are inconclusive for lesion characterization.

Accumulation of iodine-131-iodocholesterol in renal cell carcinoma adrenal metastases.

Adrenocortical scintigraphy is a useful technique for differentiating between types of nonhyperfunctioning adrenal masses. Metastatic tumors do not normally accumulate radioiodocholesterol and show discordant uptake on scintigrams. We present two patients who showed accumulation of 131I-6beta-iodomethyl-19-norcholesterol (NP59) in the adrenal metastases from renal cell carcinoma. In one patient with bilateral adrenal metastases, accumulation in the primary tumor as well as adrenal metastases was demonstrated. The adrenal metastases in both patients were resected and were histologically proven to be metastases from clear-cell renal carcinoma. Accumulation of NP59 in metastatic adrenal tumors, although a very rare finding, suggests a pitfall in the differential diagnosis of adrenal cortical tumors.

Limited significance of asymmetric adrenal visualization on dexamethasone-suppression scintigraphy.

To assess whether a single measurement of the adrenal uptake of 6 beta-[131I]-iodomethylnorcholesterol (NP-59) on constant dexamethasone suppression would allow discrimination of adenoma from normal and bilateral hyperplasia, the adrenal uptake of 6 beta-[131I]iodomethylnorcholesterol (NP-59) was determined in 50 patients with primary aldosteronism (30 adenoma, 20 hyperplasia) and in 13 with hyperandrogenism (six adenoma, seven hyperplasia). Bilateral adrenal NP-59 activity at 5 days was seen in 14 of 36 patients with adenoma (normal to adenoma ratio of greater than or equal to 0.5), whereas marked asymmetric uptake of NP-59 was seen in six of 27 patients with hyperplasia (uptake ratio of less than or equal to 0.5). Thus the level of adrenal NP-59 uptake does not alone serve to distinguish either adenoma from the normal, contralateral adrenal or the adrenal glands in bilateral hyperplasia in all cases. It appears that the pattern of adrenal imaging, early unilateral or early bilateral NP-59 activity (less than 5 days after NP-59 on 4 mg dexamethasone), best serves to separate adrenal adenoma from bilateral hyperplasia.

SPECT semiquantitative analysis of adrenocortical (131)I-6 beta iodomethyl-norcholesterol uptake to discriminate subclinical and preclinical functioning adrenal incidentaloma.

UNLABELLED: The goal of this study was to evaluate the clinical reliability of the (131)I-6 beta-iodomethyl-norcholesterol ((131)I-NP-59) uptake semiquantitative evaluation method we propose for the characterization of adrenocortical masses in a selected population of patients with disease clinically classified as subclinical (SC) and preclinical (PC) Cushing's syndrome (CS) according to Reincke's definition. METHODS: Forty-seven consecutive patients with incidentally discovered unilateral adrenal masses were examined by a triple-head SPECT system after intravenous injection of (131)I-NP-59. Abdominal SPECT was performed at 24, 48, 72, and, in selected cases, 96 h after tracer injection. Connected with adrenals and liver, a standard elliptic region of interest (ROI) was manually drawn, taking care to avoid the gallbladder region. The adrenal ROI integral count, obtained by summing the 24-, 48-, and 72-h counting values, was normalized by the hepatic integral count. Subsequently, the adrenal percentage of relative uptake (UPT%) was computed. RESULTS: Discriminant analysis was performed on the variables UPT%, adrenocorticotropic hormone (ACTH) serum concentration, and CT mass dimension (CTMD) to determine the variable, or combination thereof, best discriminating between the SC-CS and PC-CS groups. Compared with both ACTH and CTMD variables, univariate analysis confirmed the UPT% variable as the most significant to discriminate between these 2 clinical groups. In fact, UPT% alone correctly classified 8 of 9 patients in the SC-CS group and 20 of 22 patients in the PC-CS group with 95% positive and 80% negative predictive values and with overall accuracy, sensitivity, and specificity equal to 90%, 91%, and 89%, respectively. When all 3 variables were submitted to stepwise discriminant analysis, the derived classification matrix, after cross-validation, correctly classified 9 of 9 patients in the SC-CS group and 18 of 22 patients in the PC-CS group with 100% positive and 69% negative predictive values and with overall accuracy, sensitivity, and specificity equal to 87%, 82%, and 100%, respectively. CONCLUSION: According to these initial results, use of the proposed semiquantitative approach associated with both laboratory screening for cortisol production and CTMD measure seems to be able to increase the clinical diagnostic accuracy of PC-CS. This approach could be used in the follow-up of adrenal mass function every time hormonal or clinical features are suggestive of adrenocortical hyperfunction.

A new and improved synthesis of 19-iodocholesterol 3-acetate.

19-Iodocholesterol 3-acetate (VI) was synthesized in a single step by iodo group substitution for hydroxyl using either one of two different reagents: (1) carbodiimidonium methiodide (VIII) or (2) triphenyl-phosphine/N-iodosuccinimide (IX). The yields were as satisfactory as those obtained from the two step iodide replacement of a 19-hydroxy group via the 19-tosyloxy group. The principal intermediate, 19-hydroxy cholesterol 3-acetate (V), was derived in appreciable quantities, and relatively inexpensively, through the Pb (OCOCH3) 4 photolytic oxidation of the bromohydrin of cholesterol 3-acetate (III) to the epoxide (IV) thence Zn reduction to the 19-hydroxy compound. A specially designed 12 liter flask was of aid in accomplishing the photolysis reaction. Dry column chromatography with the supportive puncture sampling was integral to achieving the good yields and high purity of 19-iodocholesterol (VIII).

Distribution of 19-iodocholesterol-125I 3-acetate in the dog and the rat.

Since 19-iodocholesterol ethyl and methyl ethers and 3 beta-iodo-5-cholestene localized in dog adrenal, the distribution of 19-iodocholesterol 3-acetate was similarly studied. This ester was concentrated by the dog adrenal to the same extent as 19-iodocholesterol. Despite a previous report that the ester was not appreciably taken up by the rat adrenals, distribution experiments were undertaken, and the results showed that the ester preferentially localized in the adrenals of the rat as well as the dog.

3-Ethyl and 3-methyl ethers of 19-iodocholesterol as potential adrenal scanning agents.

19-Iodocholesterol-131I, though useful as an adrenal scanning agent, was found to be unstable. However, the substitution of methoxyl and ethoxyl groups for the hydroxyl group in the 3 position rendered these derivatives much more stable in solid form than the parent compound. They showed concentration in the adrenals of dogs similar to that of 19-iodocholesterol itself and therefore may be useful as adrenal scanning agents.

Case report: failure of adrenal scintigraphy to exhibit 131I cholesterol uptake in a CT-demonstrated, surgically proven aldosteronoma.

This is the case of a large 2 x 1.5 cm adrenal tumor demonstrated on CT scan that was proven biochemically and surgically to be an aldosteronoma and that did not concentrate 6-beta(131I)-iodo-methyl-19-norcholesterol (NP-59). Before the publication of this case, all CT-identified aldosteronomas of greater than 1 cm have concentrated NP-59. Previously, an adrenal mass of greater than 1 cm that failed to concentrate NP-59 was excluded from being an aldosteronoma. This concept must be reevaluated with the publication of this case.

Adrenocortical scintigraphy with 131I-6-beta-iodomethyl-norcholesterol (NP 59) in bilateral adrenocortical carcinoma.

A case of a 49-year-old man suffering from bilateral adrenocortical carcinoma with local and secondary rapid progression is reported. The results of adrenocortical scintigraphy (NP 59) and histological findings allowed the diagnosis. This case report and a literature review showed the importance of using adrenocortical scintigraphy as a complementary imaging procedure of CT or MR images.

Enterohepatic circulation and distribution of 131I-6 beta-iodomethyl-19-norcholesterol (NP-59).

The enterohepatic circulation and distribution of 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) was assessed in a rabbit model to examine the relative distribution of NP-59 and its metabolites. Adrenal, bile and serum samples were obtained from seven rabbits at 48 h following NP-59 administration (240 to 570 microCi) and the distribution of 131I radioactivity examined using thin layer chromatography. In serum 71% of the radioactivity circulated as NP-59 and 20% as NP-59 esters. In contrast greater than 90% of the adrenal radioactivity was in the form of NP-59 esters while in bile 70% of the activity was NP-59 with the remainder in the form of bile acids. In another group of animals, adrenal activity was observed 5 days after intragastric administration of NP-59. Thus, we have demonstrated a significant enterohepatic circulation of NP-59 that may have the potential to influence the distribution of and resultant adrenal imaging with NP-59.