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Sn-Pyrophosphate Pharmaco Kinetics and Bone Image Changes in Parathyrold Disease

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Sn-Pyrophosphate Pharmaco Kinetics and Bone Image Changes in Parathyrold Disease Technetlum-99m--Sn-Pyrophosphate Pharmaco Kinetics and Bone Image Changes In Parathyrold Disease G. T. Krishnamurthy,A. S. Brickman,and W. H. Blahd Veterans Administration Wadsworth Hospital Center and UCLA School of Medicine, Los Angeles, California Skdetal abnormalities in 12 patients with primary hyperparathyroidism, five patients with pseudohypoparathyroidism, and three patients with hypo parathyroidism were studied to compare the diagnostic sensitivity of bone radiologic examination to that of radionuclide studies using tamTc-Sn.pyro. phosphate (P9mTc-PP@) a skeletal-seeking radiopharmaceutical. The results were compared with bone mineral content as measured by the Norland Cameron densitometer. Kinetic data of the blood disappearance and plasma clearance of ssmTcpp. were obtained and compared with data of control subjects without evidence of parathyroid disease. Bone imaging with 99mTc PIJ@ may be more sensitive than routine skeletal radiographs and bone mineral analysis for the evaluation of skeletal abnormalities in patients with parathyroid disfunction. The enhancedpiasma clearance of the tracer observed in patients with primary hyperparathyroidism may reflect the direct effect of excessive parathyroid hormone on the renal handling of PsmTc-Sn@pyrophosphate. J Nuci Med 18: 236—242,1977 Bone imaging with 99'@Tc-labeled phosphate corn In the present studies scintillation imaging was per pounds has been employed most extensively for the formed with aamTc@Sn@pyrophosphate(oamTc@PPi). detection of metastatic bone lesions, primary bone Urinary excretion of unlabeled pyrophosphate has tumors, infections, Paget's disease, and other benign been reported to be increased in patients with pri lesions of bone (1—5). Application of these imaging mary hyperparathyroidism (7). Contradictory re techniques for the evaluation, diagnosis, and study sults, however, have been reported by others (8). of metabolic bone disease has been limited. The Thus, knowledge concerning the blood disappear present studies were undertaken to establish the role ance and renal clearance of 9omTc@PPj may be of of bone imaging in determining bone abnormalities diagnostic value. in patients with primary hyperparathyroidism, hypo parathyroidism, and pseudohypoparathyroidisrn. In MATERIALS AND METHODS a large series of patients, skeletal radiographs in dicated that focal skeletal lesions (e.g., Brown The specific parathyroid disorder in each patient was established by clinical, biochemical, and radio tumors, cysts, cortical or subperiosteal resorption) occur in approximately 10% of patients with pri logic evaluation, including RIA determination of mary hyperparathyroidism whereas less specific ab serum parathormone levels. Twelve patients with normalities such as generalized demineralization may be found in 30% (6) . A comparison of the rela tive sensitivity of bone roentgenography to that of Received June 21, 1976; revision accepted Nov. 24, 1976. bone imaging in the study of metabolic bone disease For reprints contact: G. T. Krishnamurthy, Nuclear Mcdi cine Service (691/172A), Veterans Administration Wads may provide additional information. worth Hospital Center, Los Angeles, CA 90073. 236 JOURNAL OF NUCLEAR MEDICINE DIAGNOSTIC NUCLEAR MEDICINE primary hyperparathyroidism were studied. Seven Blood and urine samples were collected as de of these were confirmed by histologic examination of scribed elsewhere (10—12). Plasma clearance of the lesion and the remaining five patients by gener 99@'Tc-PP1was calculated by means of the standard ally accepted criteria for the diagnosis of primary clearance formula. Urine was collected hourly for hyperparathyroidism (including hypercalcemia, ele 4 hr. For calculationof clearanceduringthe first vated parathyroid hormone levels, abnormal re hour, the plasma count at 30 mm was used. For cal sponses to oral orthophosphate loading, and histo culation of clearance at the end of the 2nd, 3rd, and logic evidence of hyperparathyroidism from iliac 4th hours, the mean plasma counts at the beginning crest bone biopsy) . Three patients had developed and end of the hour were used. hypoparathyroidism following surgery for either thy Bone roentgenograms and scintillation camera im roid or parathyroid disease (Table I ) . The duration ages were interpreted independently by the radiolo of hypoparathyroidism in these patients ranged from gists and the authors; the readers were informed of 7 to I 1 years. Each was maintained in a normocal the possible clinical diagnosis of metabolic bone dis cemic state with regular doses of 100,000—200,000 ease. Such specific skeletal abnormalities as cyst units of vitamin D2 and oral calcium supplements, and sub-periosteal resorption and such nonspecific but all had been off treatment for 1—3months at the changes as diffuse demineralization were sought for time of bone imaging and kinetics studies. In five (Table 1) . The control group consisted of six pa patients with pseudohypoparathyroidism (Table 1), tients with histologically proven malignant soft-tissue the diagnosis had been confirmed by clinical features tumors and with normal serum levels of calcium, (hypocalcemia, elevated serum PTH levels, brachy phosphorus, and alkaline phosphatase. The serum dactyly) or the failure to enhance urinary excretion parathormone levels were not measured in these of 3',S'-cyclic adenosine monophosphate during an patients, but there was no clinical or biochemical infusion of parathyroid extract. None of these pa evidence to suspect any parathyroid disease. All had tients was under vitamin D therapy at the time of normal renal function bone images, and there was these studies. no uptake of O9mTcpp1 by the primary tumor. The Bone mineral content was evaluated by means of blood disappearance and urinary excretion of aamTc@ the Norland—Cameron bone mineral analyzer. lo PP1 were also compared with four other patients, dine-125 (400 mCi) was used as the external radia who resembled the control group of patients in every tion source. Radiation, collimated to 3 mm, was respect but who in addition had metastatic lesions passed through the radius of the nondominant arm in the bone. Blood and urine clearance values were and detected on the other side of the radius with the tested by Student's t-test for statistical significance. scintillation detector. The selected arm was reposi tioned, studied two or three times, and a mean value RESULTS was calculated. Bone mineral content (gm/cm) and The clinical, biochemical, radiologic, and histo bone width (cm) were measured and their ratio logic findings in each patient are shown in Table 1. (gm/cm2) used for analysis. These results were com Eleven of 12 patients with primary hyperparathy pared with the normal values for age- and sex roidism had hypercalcemia and most of them had matched American Caucasians and considered abnor hypophosphatemia with an elevation of serum PTH. mal if a measurement fell below the 95 % confidence Of the seven patients who underwent parathyroid limit (9). surgery, four had single adenomas and three had Bone roentgenograms were obtained in all pa parathyroid hyperplasia. Five of the patients had tients. Whole-body bone images were obtained with definite elevations of alkaline phosphatase and two a scintillation camera fitted with a Div/Con collima were at the upper limits of normal. Five patients tor, with the diverging side towards the patient, 2—3 showed generalized demineralization of bone, one hr after intravenous injection of I 5 mCi of aOmTc.. patient had subperiosteal resorption in the metacar PP1. Anterior and lateral views of the skull and pals, while the remaining six patients had normal mandible, and anterior views of the feet and hands bone radiologic studies. In seven patients, focal bone were obtained; 300,000 counts were accumulated for lesions were shown by the scintillation camera im each view. The bone images were subjectively ages, and five of these patients had no corresponding graded: 1+ being equal to normal uptake; 2+, lesions by radiographic studies. The majority of le slightly increased; and 3+, markedly increased in sions were confined to distal parts of the extremities, comparison with the normal adjacent bone or the skull, and jaw bones (Table 1). contralateral normal site. A grade of zero indicated In five of 11 hyperparathyroid patients, bone mm decreased uptake. Bone uptake intensity was visually eral content in the distal third of the radius was re compared to the kidney intensity. duced compared with age- and sex-matched controls. Volume I 8, Number 3 237 KRISHNAMURTHY, BRICKMAN, AND BLAHD TABLE 1. BIOCHEMICAL, RADIOLOGIC, HISTOLOGIC, BONE MINERAL, AND BONE IMAGE CHANGES IN PARATHYROID DISEASE phorus line calcium (mg/dl) (mg/dl) PTH phos (distal Pt. Sex/ (8.8— (3.0— (<0.3 phatase TRP radius) No.Age/ RaceCalcium10.5)Phos 5.0)Alkang/ml)findingsPRIMARYHYPERPARAThYROIDISMHyperplasia,(30—85)Bone(>75%) (gm/cm5) RadiographsRadionuclideimagesSurgical 1 53/M/C 11.60 2.0 135 180 65 0.75(N) Subperiosteal Abnormal Z. E. resorption- hands++ Deminerol izatlon 2 55/M/C 11.80 2.5 0.83 85 55 0.70(L) Normal Abnormal Adenoma hands ++ 3 51/F/C 12.50 2.6 0.40 70 67 — Demineral- Abnormal, left Adenoma, Ca ization radius +++ maxillary sinus M-P joint of rt thumb ++ 4 47/M/C 11.90 4.0 076 70 86 0.89(N) Demineral Abnormal man- Refusedsurgery ization dible -f--j--j 5 58/M/C 10.80 3.4 0.62 58 88 0J8(L) Demineral Normal Surgery pending ization 6 34/M/C 1070 3.6 0.35 80 80 0.85(N) Normal Abnormal man- Furtherfollowup dible -j--j--j
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