technetium-tc-99m-gluceptate and Lymphoma

Osmotic blood-brain barrier (BBB) disruption induced by intraarterial infusion of mannitol is used in conjunction with chemotherapy to treat human brain tumors. The time course to barrier closure, or the so-called therapeutic window, has been examined in animals but little information is available in humans. The authors, therefore assessed the time course to barrier closure after osmotic BBB disruption in humans.. Disruption of the BBB was demonstrated using 99mTc-glucoheptonate (TcGH) single-photon emission computerized tomography (SPECT) scanning in 12 patients who were treated monthly with combination chemotherapy in conjunction with BBB disruption. The primary diagnosis was primary central nervous system lymphoma in seven patients and primitive neuroectodermal tumors in five. The TcGH (20 mCi) was injected at 1- to 480-minute intervals after osmotic BBB disruption, and patients underwent SPECT scanning after 4 hours. A total of 38 studies was performed. Good-to-excellent BBB disruption was obtained in 29 procedures and poor-to-moderate disruption was seen in the other nine studies. The TcGH indices correlated with the degree of BBB disruption as measured postprocedure on contrast-enhanced CT scans (r = 0.852). Mean baseline TcGH indices were 1.02+/-0.07. For the group of patients with good-to-excellent disruptions the mean indices at 1 minute postdisruption measured 2.19+/-0.18. After 40 minutes no significant change was noted (mean index 2.13+/-0.2). Then the indices declined more steeply and at 120 minutes after the disruption the index was 1.36+/-0.02. A very slow decline was noted between 120 and 240 minutes after mannitol infusion. At 240 minutes the barrier was still open for all good-to-excellent disruptions (index 1.33+/-0.08) but at 480 minutes the mean indices had returned to the baseline level.. Results of these in vivo human studies indicate that the time course to closure of the disrupted BBB for low-molecular-weight complexes is longer than previously estimated. The barrier is widely open during the first 40 minutes after osmotic BBB disruption and returns to baseline levels only after 6 to 8 hours following the induction of good or excellent disruption. These findings have important clinical implications for the design of therapeutic protocols.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood-Brain Barrier; Brain; Brain Neoplasms; Contrast Media; Diuretics, Osmotic; Female; Humans; Infusions, Intra-Arterial; Lymphoma; Male; Mannitol; Middle Aged; Molecular Weight; Neuroectodermal Tumors; Organotechnetium Compounds; Osmosis; Permeability; Radiopharmaceuticals; Sugar Acids; Time Factors; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Eighteen patients with gastrointestinal and retroperitoneal non-Hodgkin's lymphoma received abdominal radiotherapy as their primary treatment. Each patient received a total tumor dose of 2200 to 4500 cGy in 5 to 9 weeks to the whole or half of one kidney. Nine patients developed unilateral radiation nephropathy demonstrable on post-treatment evaluation with 99m Tc glucoheptonate blood flow, delayed static scan, and an I-131 radio-hippurate renal perfusion study. The tests were periodically repeated over periods ranging from 5 to 8 years. Six patients with nephropathy and 4 patients without nephropathy were followed 5 years or longer. The minimum nephro-pathogenic irradiation dose was 2200 cGy delivered in 59 days. The incidence of nephropathy is higher with increase in the total dose. Short term recovery in function was observed in 3 patients and long-term complete recovery was observed in one patient. Atrophic renal change was irreversible and progressive in 3 patients over a 6 to 7 year follow-up period. In this group of patients, an abnormal creatinine clearance and serum beta-2 microglobulin level was indicative of vascular damage. Elevated arterial blood pressure was seen in 5 patients. All were controlled medically, without nephrectomy. There was no other clinically significant problem resulting from the unilateral nephropathy in this group of patients.

Topics: Follow-Up Studies; Gastrointestinal Neoplasms; Humans; Iodohippuric Acid; Kidney; Kidney Diseases; Lymphoma; Organotechnetium Compounds; Radionuclide Imaging; Radiotherapy, High-Energy; Retroperitoneal Neoplasms; Sugar Acids; Technetium