Nonmyeloablative iodine-131 anti-B1 radioimmunotherapy as outpatient therapy

The expected effective dose equivalent to an individual from contact with 131I anti-B1 radioimmunotherapy (RIT) patients released immediately after therapeutic infusion was estimated. METHODS: Effective dose equivalents were calculated retrospectively using data acquired on 46 patients treated with 1311 anti-B1 RIT as inpatients. Effective dose equivalents to members of the public were estimated using the method published in the Nuclear Regulatory Commission (NRC) Regulatory Guide 8.39, assuming the administered activity, the patient-specific effective half-life, the 0.25 occupancy factor, and no photon attenuation. Effective dose equivalents also were estimated using ionization chamber dose rates, measured immediately after therapeutic infusion and integrated to total decay based on the measured effective half-life. RESULTS: For the whole-body treatment absorbed dose limit of 75 cGy (75 rad), the administered 131I activity ranged from 2.1 to 6.5 GBq (56 to 175 mCi), and the measured dose rate at 1 m ranged from 70 to 190 microSv/hr (7 to 19 mrem/hr). The total-body effective half-life for these patients ranged from approximately 40 to 88 hr. Using the NRC method and not accounting for the attenuation of photons, the mean dose equivalent to the public exposed to an 131I anti-B1 patient discharged without hospitalization was 4.9 +/- 0.9 mSv (490 +/- 90 mrem). The range was 3.2-6.6 mSv (320 to 660 mrem), where 48% of patients would deliver a dose to another individual that is <5 mSv (500 mrem) (i.e., 48% of the patients would be allowed to return home immediately following the infusion). Using the measured dose rate method, the mean dose equivalent to an individual exposed to the same RIT patients was 2.9 +/- 0.4 mSv (290 +/- 40 mrem). The range was 2.0-3.7 mSv (200-370 mrem), where 100% of the estimated effective dose equivalents were <5 mSv (500 mrem). CONCLUSION: Based on calculated and patient-specific exposure data, outpatient RIT with nonmyeloablative doses of 131I should be feasible for all patients under current NRC regulations. Implementing outpatient RIT should make the therapy more widely available and more convenient and should lower patient care costs without exceeding accepted limits for public exposure to radiation.     

Remotely pollable Geiger-Müller detector for continuous monitoring of iodine-131 therapy patients

In many countries, patients treated with therapeutic amounts of (131)I are hospitalized because of radiation safety considerations. To determine when they can return home, radiation levels are intermittently monitored at bedside using a handheld Geiger-MIller (GM) counter, although this procedure can be cumbersome and inexact. METHODS: We have developed and tested a remotely pollable system for continuous radiation monitoring of (131)I therapy inpatients, using readily available hardware and standard telephone lines. The remote detector system, consisting of a palmtop IBM-compatible personal computer, specialized software, PCMCIA modem and miniature serial port-based GM detector, is placed opposite the patient's bed at a fixed distance, and continuous 1-min acquisitions are started. Initially and at least twice daily, the remote palmtop is contacted by modem, and all interval data are uploaded onto the operator's base computer over the telephone line, including measurements taken with the patient in a predetermined standardized position. Continuous minute-to-minute data may be viewed in native form or can be imported into graphing and spreadsheet programs. Points acquired with the patient in standardized position are specially marked to highlight the constant geometry used. The ratio of initial counting rate to administered dose is used to estimate residual (131)I body burden by proportionality. Display of data as a semilogarithmic plot facilitates extrapolation of the activity curves and prediction of the patient's earliest time of discharge. RESULTS: We have characterized the remote GM detector system to confirm accuracy, counting rate linearity and reliability of data transfer. We describe examples that illustrate the applicability and usefulness of this method for remote monitoring of inpatient (131)I therapy levels. CONCLUSION: Monitoring patients with the described remotely pollable GM detector is an accurate and easy-to-implement technique that could conceivably lead to shortened hospital stays for (131)I therapy inpatients. Continuous quantitative data obtained are useful for kinetic and dosimetric analyses, which may be applied to study other gamma-emitting radiopharmaceuticals as well. The flexibility of the technique may permit its use in the monitoring of therapy on an outpatient basis, where allowed.     

Transient hypothyroidism

To investigate the seroprevalence of HTLV-I in Kanagawa Prefecture (central Japan), we tested the sera of 8,264 healthy volunteers and 2,414 pregnant women. Of the 8,264 healthy volunteers, 66 (0.80%) were seropositive. The seroprevalence of HTLV-I in the pregnant women was 14/2,414 (0.58%), and this rate was almost identical to that in the healthy female volunteers 15 to 44 years of age (0.59%). These figures indicate that the seroprevalence of HTLV-I in Kanagawa Prefecture is very low and that sexual contact may not be an important contributory factor.     

Bivalent hapten-bearing peptides designed for iodine-131 pretargeted radioimmunotherapy

BACKGROUND: Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. AIMS: To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. PATIENTS: Consecutive patients with acute variceal haemorrhage. METHODS: Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 pg/h octreotide (n = 73), or emergency sclerotherapy (n = 77). RESULTS: Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p = 0.06). CONCLUSIONS: The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment.     

Adrenocortical SPECT using iodine-131 NP-59

Adrenal scintigraphy with 131I-labeled 6-beta-iodomethyl-19-norcholesterol (NP-59) is a technically demanding and complex procedure. However, it can provide crucial and unique information about the functional status of the adrenal glands and guide the appropriate therapeutic management of patients with biochemically proven disease. Since the introduction of this new investigational drug, scintigraphic imaging has been performed using conventional planar techniques. We present an interesting case of primary aldosteronism in which planar scintigraphy and SPECT were combined in an attempt to increase the sensitivity of the study. SPECT revealed scintigraphic evidence of bilateral adrenocortical hyperplasia. Interestingly, the CT scan of this patient showed only an equivocal abnormality in the left adrenal gland, suggestive of an adenoma.     

Leukaemias and cancers following iodine-131 administration for thyroid cancer

We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).     

Energy-based scatter corrections for scintillation camera images of iodine-131

The use of high-dose 131I antibody therapy requires accurate measurement of normal tissue uptake to optimize the therapeutic dose. One of the factors limiting the accuracy of such measurements is scatter and collimator septal penetration. This study evaluated two classes of energy-based scatter corrections for quantitative 131I imaging: window-based and spectrum-fitting. METHODS: The window-based approaches estimate scatter from data in two or three energy windows placed on either side of the 364-keV photopeak using empirical weighting factors. A set of images from spheres in an elliptical phantom were used to evaluate each of the window-based corrections. The spectrum-fitting technique estimates detected scatter at each pixel by fitting the observed energy spectrum with a function that models the photopeak and scatter, and which incorporates the response function of the camera. This technique was evaluated using a set of Rollo phantom images. RESULTS: All of the window-based methods performed significantly better than a single photopeak window (338-389 keV), but the weighting factors were found to depend on the object being imaged. For images contaminated with scatter, the spectrum-fitting method significantly improved quantitation over photopeak windowing. Little difference, however, between any of the methods was observed for images containing small amounts of scatter. CONCLUSION: Most clinical 131I imaging protocols will benefit from qualitative and quantitative improvements provided by the spectrum-fitting scatter correction. The technique offers the practical advantage that it does not require phantom-based calibrations. Finally, our results suggest that septal penetration and scatter in the collimator and other detector-head components are important sources of error in quantitative 131I images.     

Improved cardiac iodine-123 metaiodobenzylguanidine accumulation after drug therapy in a patient with Parkinson's disease

A 72-year-old woman with Parkinson's disease and autonomic dysfunction underwent I-123 MIBG cardiac imaging to study sympathetic neuronal integrity. This revealed a defect in the infero-posterior wall. Tc-99m sestamibi myocardial perfusion imaging revealed no abnormalities. On follow-up I-123 MIBG SPECT, the defect was less prominent and the parkinsonian symptoms were ameliorated by drug therapy. Cardiac I-123 MIBG imaging may be a promising new method for evaluating drug therapy in patients with Parkinson's disease.     

Thallium-201 scintigraphy to predict therapeutic outcome of iodine-131 therapy of metastatic thyroid carcinoma

We studied the relationship between 201Tl uptake and the efficacy of radioiodine therapy in thyroid carcinoma. METHODS: Forty-four patients with metastases of well-differentiated thyroid carcinoma received 201Tl scintigraphy within the 2 mo before their initial 131I therapy. Patients were classified into two groups according to the tumor-to-background (T/B) ratio on the late 201Tl scan: high 201Tl uptake (T/B > or = 2.1) and low 201Tl uptake (T/B < 2.1). The therapeutic outcome was judged by the percent reduction in the tumor diameter at 6 mo after the treatment. The treatment was defined as effective when the tumor showed more than 50% reduction in the tumor diameter. The patients in whom radioiodine was ineffective were followed up to determine if the tumor showed further growth. RESULTS: Of the 44 patients, 25 had high 201Tl uptake and 19 had low 201Tl uptake. The therapy was effective in 15 patients and was ineffective in 29. All the patients in whom radioiodine was effective had low 201Tl uptake. On the other hand, 25 of 29 patients in whom radioiodine was ineffective had high 201Tl uptake. Eight patients, in whom radioiodine was ineffective despite good 131I uptake, had high 201Tl uptake. There were no significant differences in the positive predictive value and the negative predictive value for effective treatment between 201Tl scintigraphy and therapeutic dose 131I scintigraphy. Among the 25 patients in whom radioiodine was ineffective and who had high 201Tl uptake, the tumor diameter increased in 7 (28%). However, none of the tumors with low 201Tl uptake increased in size during the follow-up period. CONCLUSION: Thallium-201 scintigraphy has a high predictive value for the efficacy of radioiodine therapy in metastatic thyroid carcinoma. Thus, it is helpful in determining the indication for radioiodine therapy and it seems to be an adjunct to tracer dose 131I scintigraphy.     

Thymic uptake of iodine-131 in the anterior mediastinum

Two thyroidectomized patients with a history of differentiated thyroid carcinoma are presented who had nonmetastatic mediastinal 131I uptake following therapeutic doses of 131I. Chest CT scans in both patients demonstrated an anterior mediastinal mass. Surgical excision in one patient and a percutaneous CT-guided fine needle aspiration biopsy in the other disclosed normal thymus tissue. Iodine-131 uptake in the anterior mediastinum in patients thyroidectomized for follicular or papillary thyroid carcinoma may represent the thymus.     

Acute effect of inorganic iodide after 131I therapy for hyperthyroidism

Patients treated with inorganic iodide weeks to years following 131I therapy for hyperthyroidism do not adapt to its antithyroid effect. To determine whether such adaptation occurs soon after 131I therapy, serum thyroxine (T4) and triiodothyronine (T3) concentrations were measured daily for 9-14 days following 131I therapy in seventeen hyperthyroid patients. Nine patients received 150 mg KI daily starting 48 h after 131I administration; eight received only 131I. Serum T4 and T3 concentrations did not change significantly in the patients who received only 131I. In the patients who received 131I and KI, serum T4 and T3 concentrations fell promptly, reaching nadir values 2-10 days after initiation of iodide, and then increased despite continuation of KI therapy. The mean maximal fall in serum T4 was 34% and in serum T3 42%. These results show that "escape" from the acute anti-thyroid effect of iodide occurs when it is given immediately after 131I therapy, thus limiting the utility of iodide as a therapeutic agent at this time.     

Locally increased uptake of fluorine-18-fluorodeoxyglucose after intracavitary administration of iodine-131-labeled antibody for primary brain tumors

After the intracavitary administration of 131I-labeled monoclonal antibody for treatment of primary brain tumors after surgical resection, a persistent rim of 18F-fluorodeoxyglucose (FDG) accumulation surrounding the cavity can be observed on PET. This rim, although it accumulates more FDG than adjacent normal brain tissue, is not necessarily associated with tumor. In our study, we examine the characteristics of the rim that indicate persistent tumor and tumor progression. METHODS: Sequential PET studies obtained after treatment in 10 patients were reviewed and the results correlated with dosimetry and post-treatment histologic diagnoses. RESULTS: The rim of FDG accumulation was seen on the first post-treatment scan obtained 1-3 mo after therapy and persisted unchanged over the 2-26 mo follow-up period. Pathologically, the nonmalignant rim was associated with marked increase of macrophage infiltrates. Nodularity of the rim was associated with tumor. CONCLUSION: Our study demonstrates that a rim of FDG accumulation is seen after intracavitary administration of 131I-labeled monoclonal antibody therapy independent of the presence of malignant disease. Malignant recurrence is suggested by the development of new nodularity in the rim of FDG accumulation.     

Pseudotumor cerebri in an infant after L-thyroxine therapy for transient neonatal hypothyroidism

Pseudotumor cerebri is generally a benign disorder. It has been reported to occur in hypothyroidism, particularly after the initiation of L-thyroxine replacement therapy. Previous case reports have involved children primarily in the peripubertal age range (approximately 8 to 13 years). We report here the development of pseudotumor cerebri in an infant who required treatment with L-thyroxine for transient neonatal hypothyroidism as a result of maternal thyroid-stimulating hormone receptor-blocking antibodies.     

False-positive whole-body iodine-131 scan due to intrahepatic duct dilatation

Focal retention of radioactivity in the liver on whole-body 131I scan was interpreted as a metastatic lesion in a patient with well-differentiated thyroid cancer. Intrahepatic duct dilatation, usually resulting from biliary tract obstruction by bile stone, is a common disorder and may cause bile stasis. A patient with papillary thyroid cancer and a previous history of biliary tract stones had focal retention of radioactivity in the liver on whole-body 131I scan. Abdominal CT, endoscopic retrograde cholagiopancreatography, radionuclide cholangiography and sequential 131I scans demonstrated that this focal retention of radioactivity was caused by intrahepatic duct dilatation. Focal retention of radioactivity is visualized on delayed images but not on early images. The radioactivity initially increases and then decreases on following days.     

Radioimmunotherapy of medullary thyroid cancer with iodine-131-labeled anti-CEA antibodies

This study evaluates the pharmacokinetics, dosimetry, toxicity and therapeutic potential of radiolabeled NP-4 and MN-14 anti-CEA antibodies in medullary thyroid cancer (MTC). METHODS: Eighteen patients with advanced MTC entered exploratory clinical studies with therapeutic doses of 131I-labeled NP-4 and MN-14 murine monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). Doses administered ranged from 46 mCi for 131I-MN-14 lgG to 195 mCi for 131I-MN-14 F(ab)2 in patients negative for human anti-mouse antibodies (HAMA). RESULTS: The radioconjugate blood half-life (T1/2) for the whole lgG was 42.5+/-5.0 hr compared to 18.8+/- 4.1 hr for the bivalent fragments. Tumor doses of 17.5+/-11.0 and 11.4+/-6.3 cGy/mCi were estimated for 131I-MN-14 lgG and F(ab)2, respectively. Tumor/red marrow dose ratios exceeded 3:1 for most lesions. Red marrow doses of up to 350 cGy generally could be delivered with < grade 4 toxicity. Seven of 14 evaluable patients showed evidence of anti-tumor effects lasting up to 26 months, based on physical exam, tumor markers or computed tomography. CONCLUSION: This study demonstrates that anti-CEA MAbs may be suitable for radioimmunotherapy of metastatic or recurrent MTC.